Postdexamethasone Cortisol Research Articles

Acute Confusional State (Delirium) Soon after Stroke is Associated with Hypercortisolism

Acute confusional state (ACS), or delirium according to DSM-III-R, and the function of the hypothalamic-pituitary-adrenal-axis were studied in 83 patients soon after an ischemic supratentorial stroke. ACS was common (35/83 = 42%). Patients with stroke had higher cortisol levels after dexamethasone than an elderly healthy control population (median = 75 and 31 nmol/l, respectively; p < 0.001). The stroke patients with ACS had higher post-dexamethasone cortisol levels than stroke patients without ACS (median = 98 vs. 59 nmol/l; p < 0.001). A logistic regression analysis revealed that ACS in stroke patients was independently associated with high cortisol levels after dexamethasone, extensive motor impairment and left-sided brain lesion. There is a close association between ACS and hypercortisolism in stroke patients, not explained by other known determinants of ACS. The possibility that hypercortisolism is involved in the pathophysiology of confusion caused by an acute stroke should be considered.

Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke.

Hypercortisolism is common in stroke patients. The aim of this study was to investigate possible disturbances at different sites within the hypothalamic-pituitary-adrenal axis. We also studied possible associations between hypercortisolism and clinical manifestations of brain dysfunction. Patients with an acute ischemic stroke (n = 16; mean +/- SD age, 71 +/- 11 years) were compared with healthy elderly subjects (n = 9). We performed a short adrenocorticotropic hormone (ACTH) test with 0.25 mg 1-24 ACTH injected intravenously and an overnight dexamethasone suppression test with 1 mg dexamethasone given orally at 11 PM. Serum cortisol levels after dexamethasone at 8 AM were significantly higher in stroke patients (p = 0.003). The area under the curve for the cortisol response to ACTH was elevated in seven (47%) of stroke patients, and the centered cumulative cortisol response was elevated in three (20%) patients. The area under the curve response correlated significantly to the presence of an acute confusional state and male sex in stroke patients (rs = 0.63 and rs = 0.62, respectively; p < 0.05), whereas the centered cumulative cortisol response diminished with increasing age (rs = -0.62; p < 0.05). Postdexamethasone cortisol levels were significantly correlated to the presence of an acute confusional state and to extensive limb paresis (rs = 0.66 and rs = 0.62, respectively; p < 0.05). There are abnormalities in the cortisol axis both at the central level and at the adrenal level early after stroke. Hypercortisolism is closely associated with cognitive disturbances and extensive motor impairment.

The Dexamethasone Suppression Test in children and adolescents: A review and a controlled study

Dexamethasone Suppression Test (DST) studies conducted in children and adolescents are reviewed, together with factors hypothesized to explain discrepancies in rates of DST nonsuppression across studies. These factors are then examined in a controlled study of 27 adolescents with major depressive disorder (MDD) and 34 normal controls (NC). subjects were given 1 mg of dexamethasone at 11:00 pm, and the following day serum samples for cortisol were collected each hr from 8 am to 11 pm through an indwelling catheter. There were no significant differences found between the MDD and NC subjects on any postdexamethasone cortisol measure. Further, cortisol suppressors and nonsuppressors were not distinguished by any of the hypothesized factors identified from the review, including inpatient status, presence of suicidality, endogenous features, psychotic symptoms, or prior history of MDD. Questions about the appropriateness of the 1 mg dose of dexamethasone (currently the standard dose used with adolescents) are raised, together with a discussion of the effects of stress on DST findings.

Adrenocorticotropin hormone, beta-endorphin and cortisol responses to oCRF in melancholic patients.

Several authors have reported attenuated adrenocorticotropin hormone (ACTH) responses to corticotropin releasing factor (CRF) administration in melancholic patients as compared with healthy controls. In order to explore the integrity of the hypothalamic-pituitary-adrenal (HPA)-axis in melancholics, we examined the following parameters in 98 subjects: the ACTH; beta-endorphin; and cortisol responses to ovine CRF (oCRF) (100 micrograms/i.v.); and the postdexamethasone cortisol values. We found significant lower CRF-induced ACTH responses in melancholic patients as opposed to healthy controls and minor depressives, while major depressives occupied an intermediate position. The psychopathological correlates of the blunted CRF-induced ACTH responses were feelings of worthlessness, self-reproach, or excessive guilt. The CRF-stimulated beta-endorphin and cortisol response did not differ between the study samples. Higher baseline plasma cortisol was associated with attenuated CRF-induced ACTH responses, but these effects were not pertinent to melancholia. There were no relationships between the disordered oCRF test results, and postdexamethasone cortisol values, age, body size, sex and severity of illness. The diagnostic power of the oCRF and the dexamethasone suppression test for melancholia is enhanced when both test results are combined.

Biological correlates of the Newcastle Scale in depressive illness: a multivariate approach.

Rapid eye movement latency (RL), delta max thyroid-stimulating hormone (dmTSH) and 1600 (DST16) and 2300 (DST23) post-dexamethasone cortisol values were determined in a group of 93 depressed patients who were assessed with the Newcastle Endogenous Depression Diagnostic Index (NEDDI). After the effects of age, gender and severity of illness were controlled for, stepwise multiple regression showed that depressive psychomotor activity and weight loss were the 2 NEDDI items most contributing to explain DST23 variance, as was depressive psychomotor activity for dmTSH variance. When the depressive sample was dichotomized according to the presence of these 2 items, the 2 groups had significantly different DST16, DST23, dmTSH and RL values. This suggests that weight loss, agitation and retardation could represent a core feature of a biologically mediated depressive subtype.

Prediction of Suicidal Behavior from Biologic Tests

Biochemical studies related with suicidal behavior have mainly dealt with monoaminergic and corticosteroidal measures. We used some of these measures in a study of 61 suicide attempters who, except for occasional doses of benzodiazepines, had been medication free for a mean of 16 days. The monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in lumbar cerebrospinal fluid (CSF). We found that violent suicide attempters (N = 18) had 5-hydroxyindoleacetic acid concentrations below the median of all patients, whereas the concentrations of 3-methoxy-4-hydroxyphenylglycol were mainly above the median. We found no significant differences between violent and nonviolent (N = 43) attempters concerning CSF homovanillic acid, 24-hour urinary norepinephrine-epinephrine and cortisol, activity of monoamine oxidase in platelets, or post-dexamethasone plasma cortisol. Four patients completed suicide, and 3 of them had CSF 5-hydroxyindoleacetic acid concentrations at or below the median. All completed suicides had CSF 3-methoxy-4-hydroxyphenylglycol concentrations above the median. Urinary measures and platelet monoamine oxidase activity of completed suicides were in the higher concentration ranges. Patients who repeated suicidal behavior after the index investigation had low 24-hour urinary cortisol levels more often than those who did not repeat. Because our subgroups of patients are small, we cannot draw any firm conclusions about the value of our CSF and urinary biochemical findings predicting suicidal behavior. However, our CSF findings in violent suicide attempters are similar to those observed in other studies.

Agitation and postdexamethasone cortisol levels in Alzheimer's disease

The clinical correlates of hypothalamic-pituitary-adrenal (HPA) functioning were examined in 29 patients with probable Alzheimer's disease. The 8:00 a.m. postdexamethasone cortisol levels of these patients were highly correlated with higher agitation scores but not with the degree of depressed mood or memory impairment. The possible neural basis for the association between hypercortisolism and behavioral disturbance in Alzheimer's disease warrants further exploration and replication.

A longitudinal study of plasma cortisol and depressive symptomatology by random regression analysis

The authors utilized a random regression model to test the longitudinal relationship between depressive symptomatology and plasma cortisol levels obtained before and after the administration of dexamethasone in 62 affectively ill inpatients. This statistical model for longitudinal studies permits the inclusion of subjects with incomplete data as well as subjects measured at different time points. The most significant relationshps were found between decreases in depressive symptoms and decreases in the 8:30 AM predexamethasone and the 4:00 PM postdexamethasone cortisol values. Patients were also classified as responders or nonresponders, and the rate of change in several plasma cortisol measures were separately analyzed for these two groups. No differences in the rate of change in plasma cortisol levels were found between responders and nonresponders. These results suggest that the decreases in cortisol production associated with clinical improvement may be partially explained by a regression toward the mean effect. Some of the possible explanations for these results are discussed.

Seasonal variations of the dexamethasone suppression test in depression compared with schizophrenia: a gender effect

The circannual results of the dexamethasone suppression test (DST) were compared in depressed and schizophrenic patients for the periods November–February and March–October. During the winter months, female depressive and schizophrenic patients had lower rates of DST nonsuppression as well as lower concentrations of post-dexamethasone plasma cortisol, compared to the March–October period, despite similar pre-dexamethasone cortisol levels. Male depressed patients had lower pre-dexamethasone cortisol levels during the winter months while male schizophrenics had higher pre- and post-dexamethasone cortisol levels and higher rates of DST nonsuppression. This may suggest less disturbance of HPA axis function in winter months in depressed patients, mostly females, and confirms findings from some previous studies. A gender effect of DST seasonality was also demonstrated, with male schizophrenic patients presenting a reverse DST nonsuppression pattern compared with female schizophrenic patients.

Effect of Citalopram, a Selective 5‐HT Reuptake Blocker, in Emotionally Disturbed Patients with Dementiaa

In patients with Alzheimer's disease and vascular dementia, there are symptoms not only of cognitive impairment but also of emotional disturbance. Postmortem human brain studies have shown a disturbed metabolism of serotonin and overactivity of neuroendocrine-controlling factors in the hypothalamus. Treatment with a selective 5-HT reuptake blocker, citalopram, causes a significant reduction in postdexamethasone cortisol levels. Citalopram in patients with dementia disorders produces no improvement in psychomotor and cognitive behavior, but symptoms of emotional disturbance are reduced. Citalopram does not have a pure antidepressant effect; rather, the drug is considered an emotional stabilizer.

Incidence of hypercortisolism and dexamethasone resistance increases with age among wild baboons

While many features of the adrenocortical axis are unchanged with age in humans, there is a pattern of senescent hypercortisolism. This occurs basally, following threshold doses of dexamethasone, and in synergy with depression or Alzheimer's disease. An understanding of neuroendocrine aging is important, for both its gerontological implications, and determination of normative values for comparison with neuropsychiatric states. We have investigated whether aging is associated with hypercortisolism in a population of wild primates. The subjects were 108 yellow baboons ( Papio cynocephalus) that have been under long-term study of Amboseli National Park in Kenya. Animals were anesthetized by blowgun under similar circumstances that allow for determination of basal cortisol concentrations. Sixty minutes later, 5.0 mg dexamethasone was administered to each animal, and cortisol determinations were made on serum collected immediately before administration and 6 hr later. Basal cortisol concentrations rose with age ( p < 0.028; r = 0.23). This occurred in a nonprogressive manner, in that there were no differences in concentrations among the youngest three quartiles of animals, whereas animals in the oldest quartile (older than approximately 16 years) had significantly higher values. In addition, there was a significant increase in postdexamethasone cortisol concentrations with age ( p < 0.01; r = 0.31). This feature emerged progressively with age in both sexes. A number of possible artifactual causes of this senescent pattern could be eliminated, including medication confound, coincident disease, and body weight. These findings suggest that hypercortisolism and glucocorticoid feedback resistance might be general features of primate aging.

Higher postdexamethasone serum cortisol levels in agoraphobic than in nonagoraphobic panic disorder patients

The dexamethasone suppresion test (DST) was performed in panic disorder (PD) patients with (n = 32) or without (n = 31) agoraphobia and in normal controls (n = 49). Postdexamethasone serum cortisol levels were significantly higher in agoraphobic PD patients (105.3 ± 19.3 nmol/L) both when compared to PD patients withput agoraphobia (47.3 ± 7.7 nmol/L; p < 0.01) and when compared to healthy controls (51.7 ± 8.3 nmol/L; p < 0.01). The rate of nonsuppressors (i.e., subjects displaying postdexamethasone cortisol levels > 138 nmol/L) was 28% and 3% in agoraphobic and nonagoraphobic PD patients, respectively, and 12% in controls. In patients, the postdexamethasone cortisol levels did not correlate with the number of panic attacks per week, baseline anxiety as measured using the Hamilton Anxiety Scale, depressive symptoms as measured using the Montgomery-Åsberg Depression scale, or duration of illness. Data from eight patients in whom a second DST was performed after treatment with imipramine or clomipramine for three months indicate that a marked reduction of the number of anxiety attacks is not necessarily accompanied by a normalization of pathological DST. In conclusion, it is suggested that the elevated postdexamethasone cortisol levels sometimes observed in agoraphobic PD patients are more closely related to the agoraphobic behavior than to the panic attacks per se.

Neuroendocrine Challenge Studies in Puerperal Psychoses

Subjects admitted to hospital with post-partum psychoses were compared with matched normal post-partum controls using two neuroendocrine challenge tests: dexamethasone suppression of cortisol and TRH stimulation of TSH. Post-dexamethasone cortisol levels were significantly elevated. There were less-clear hints of blunting of TSH response. In the small samples there was no obvious association of abnormalities with any particular diagnoses within the range of mania, psychotic depression and schizoaffective disorders.

Abnormal pituitary function during melancholia: Reduced α-melanocyte-stimulating hormone secretion and increased intact ACTH non-suppression

In order to investigate pituitary α-melanocyte-stimulating hormone (α-MSH), intact (1–39 structure) adrenocorticotropic hormone (ACTH), and adrenal cortisol secretion, we measured 8 a.m. plasma levels of those hormones before and after administration of 1 mg dexamethasone in 39 depressed inpatients and 10 healthy controls. We found a significantly lower baseline α-MSH secretion in melancholic patients as opposed to healthy controls. There were no significant relations between α-MSH secretion on the one hand and ACTH or cortisol secretion on the other. Dexamethasone did not affect the 8 a.m. α-MSH circulating levels. The post-dexamethasone intact ACTH and cortisol values were significantly higher in melancholics as compared with healthy, minor and simple major depressed subjects. ACTH non-suppression was defined as post-dexamethasone intact ACTH ⩾ 12 pg/ml. ACTH non-suppression was found to be more sensitive (70%) and specific (100%) for melancholia than cortisol non-suppression. By means of pathway analysis we have established that cortisol non-suppression during a severe depression is completely determined by an augmented ACTH escape from suppression by dexamethasone. It is concluded that the assay of post-dexamethasone intact ACTH could, in the future, replace post-dexamethasone cortisol determination.

Serial Dexamethasone Suppression Tests and Plasma Dexamethasone Levels

Serial 1-mg dexamethasone suppression tests with concurrent plasma dexamethasone assessments were conducted in 58 patients with endogenous depression treated with electroconvulsive therapy (ECT). Plasma cortisol levels decreased significantly from pretreatment to immediately posttreatment, and they declined further during the first week after the ECT course, when patients remained drug free. Plasma dexamethasone levels showed an opposite pattern of progressive increases over these three time points. The progressive changes in plasma dexamethasone and cortisol levels seen during the week after ECT indicate that alterations in the bioavailability of dexamethasone and in hypothalamic-pituitary-adrenal axis function may be incomplete immediately after the ECT course. This may partly account for previous inconsistencies in serial dexamethasone suppression test findings with this treatment modality. The major finding was that clinical response was associated with increased plasma dexamethasone levels, whereas changes in cortisol levels were independent of clinical outcome. With ECT, changes in plasma dexamethasone levels may be more related to changes in clinical state than changes in postdexamethasone cortisol levels. The extent to which clinical recovery with other treatments in depression is associated with altered bioavailability of dexamethasone and perhaps other compounds is unknown and in need of investigation.

Cognitive impairment and symptomatology associated with postdexamethasone cortisol concentrations in unmedicated schizophrenic patients

The urinary excretion of biopterin and neopterin, pterin compounds related to tetrahydrobiopterin, the cofactor for the initial steps in monoamine synthesis, was serially measured in a heterogeneous group of psychiatric patients and compared to excretion in control subjects, to state of illness, and to the results of the dexamethasone suppression test. Patients with major depression had increased excretion of biopterin compared to normal subjects. There was no relationship between biopterin or neopterin excretion and postdexamethasone cortisol levels. Pterin excretion did not significantly change with improvement in mood or with conversion from nonsuppressor to suppressor status. The meaning of increased urinary biopterin is presently unclear, although its relation to hormonal state and sympathoadrenal tone deserves further study.

Symptomatology and cognitive impairment associate independently with post-dexamethasone cortisol concentrations in unmedicated schizophrenic patients

Serum cortisol concentrations were measured after dexamethasone administration (1 mg) in 21 neuroleptic-free schizophrenic inpatients. Patients were assessed using the Brief Psychiatric Rating Scale and a battery of cognitive tests. A significant correlation was found between negative symptoms and both 8:00 AM and 4:00 PM post-dexamethasone cortisol concentration (PDC). Cognitive impairment on several measures was also correlated with 8 AM PDC, but in an independent manner. Although positive and negative symptoms were unrelated, exploratory analysis revealed a significant inverse correlation between a positive symptom grouping and both 8:00 AM and 4:00 PM PDC.

Postdexamethasone cortisol predicts agitation but not rate of progression in Alzheimer's disease : Brian A. Lawlor, M.D., Peter Aupperle, M.D., Richard C. Mohs, Ph.D., Gabriel Tsubuyama, M.D., Bonnie M. Davis, M.D., Michael Davidson, M.D., and Kenneth L. Davis, M.D. Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029

Postdexamethasone cortisol predicts agitation but not rate of progression in Alzheimer's disease : Brian A. Lawlor, M.D., Peter Aupperle, M.D., Richard C. Mohs, Ph.D., Gabriel Tsubuyama, M.D., Bonnie M. Davis, M.D., Michael Davidson, M.D., and Kenneth L. Davis, M.D. Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029

Dexamethasone suppression test in schizophrenia: Relationship to symptomatology, ventricular enlargement, and outcome

To relieve confusion about the clinical correlates and prognostic implications of the dexamethasone suppression test (DST) in schizophrenia, we conducted a DST in 44 schizophrenic inpatients at drug-free baseline and approximately 4 weeks after neuroleptic treatment. Patients were rated on positive, negative, and depressive symptoms at both times. A head computed tomography (CT) scan was performed and measures of ventricle-brain ratio (VBR) obtained. Clinical improvement was monitored at four weeks, and longer-term outcome assessed at 1 year. Seventeen of the 44 patients were DST nonsuppressors at baseline, and five of these remained nonsuppressors at 4 weeks posttreatment. Postdexamethasone plasma cortisol levels were correlated with negative symptoms at baseline (r = 0.45; p less than 0.01), but not after 4 weeks of neuroleptic treatment. Postdexamethasone plasma cortisols were not related to global severity, positive, or depressive symptoms at either timepoint or to VBR. Persistent nonsuppression was associated with poor outcome, but baseline postdexamethasone cortisol levels were unrelated to outcome at 4 weeks and 1 year. The literature on DST in schizophrenia is reviewed and attempts are made to reconcile discrepant findings and to discuss pathophysiological implications.

L-5-hydroxytryptophan stimulated cortisol escape from dexamethasone suppression in melancholic patients

The dexamethasone suppression test (DST) was carried out in 62 depressed patients. At 0800 the postdexamethasone cortisol values were determined and 125 mg L-5-hydroxytryptophan (L-5-HTP) was administered. The second cortisol sample at 0930 revealed a significant enhancing effect for L-5-HTP on the postdexamethasone cortisol values in melancholic patients, whereas no effects were detected in minor depressives. Our results show that L-5-HTP converts some DST suppressors into nonsuppressors, whereas the escape from dexamethasone in some nonsuppressors is markedly stimulated. The L-5-HTP-stimulated 0930 postdexamethasone cortisol values performed markedly better than the 0800 DST results: at a cut-off value of greater than or equal to 5 micrograms/dl the sensitivity for melancholia increased from 46% to 68%, and the specificity remained unchanged (96%).