The combined dexamethasone/CRH test: A refined laboratory test for psychiatric disorders

Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany
Journal of Psychiatric Research (Impact Factor: 4.09). 07/1994; 28(4):341-356. DOI: 10.1016/0022-3956(94)90017-5

ABSTRACT This report summarizes our extensive experience with the application of the DEX/CRH test to assess hypothalamic-pituitary-adrenal-system (HPA) alteration in patients with psychiatric disorders. The application of this combined dexamethasone suppression/CRH-challenge (DEX/CRH) test requires individuals to take 1.5 mg dexamethasone (DEX) at 23:00 h orally the previous night. On the day of the test, 100 μg human CRH are administered to the subjects under study at 15:00 h intravenously as a bolus, and blood samples for the determination of plasma cortisol and ACTH are drawn every 15 min from 14:00 h to 18:00 h. DEX/CRH-test results from 96 patients with major depression (MDE), 11 with a manic episode (MA), 9 with panic disorder (PD), 24 with a schizophrenic psychosis (SP), and 82 healthy control subjects served as the data base for this report. Three major conclusions can be drawn from statistical analysis of these data: 1. Psychiatric patients (n = 140), regardless of diagnostic classification, release significantly more cortisol and ACTH after DEX and additional CRH in comparison with age-matshed controls. This hormonal release pattern (DEX/CRH-test phenomenon) supports the assumption that psychiatric patients are prone to an altered glucocorticoid feedback regulation during the acute illness episode. This supports the notion that the DEX/CRH-test phenomenon constitutes a neuroendocrine sign of these various disorders and emphasizes the usefulness of the DEX/CRH test as a laboratory test to monitor the course of these disorders. 2. The sensitivity of the DEX/CRH test for MDE (about 80%) greatly exceeds that of the standard DST (1–2 mg of DEX), which has been reported to average about 44% in a meta-analysis of the literature data; in our sample the sensitivity of the DST was about 25%. 3. The sensitivity of the DEX/CRH test can be further increased to above 90% if subjects are clustered into four different age ranges: age < 35 years, age between 35 and 50 years, age between 50 and 70 years, and age above 70 years. 4. By reducing the time points of blood sampling for ACTH and cortisol to as few as five (15:00, 15:30, 15:45, 16:00, and 16:15 h), the DEX/CRH-test procedure becomes more convenient and more easily applicable without reducing its sensitivity.

  • [Show abstract] [Hide abstract]
    ABSTRACT: A number of studies have suggested that the metabolic syndrome (principally, the combination of hypertension, glucose intolerance, and dyslipidemia) is associated with subtle dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis leading to raised circulating cortisol concentrations. The mechanisms underlying these observations are not known. We assessed the salivary cortisol response to awakening and pituitary-adrenal responses during a 100-μg human corticotrophin-releasing hormone (CRH) test and a dexamethasone-suppressed CRH test in a well-characterized group of 65-year-old men (n = 122). In the cohort from which this subgroup was drawn, there were associations between the components of the metabolic syndrome and 9 am cortisol concentration in line with previous studies. However, there were no significant associations between blood pressure, glucose tolerance, and lipid concentrations and the dynamic tests of HPA activity. We therefore found no evidence to suggest that exaggerated pituitary responsiveness or increased central drive to the pituitary, as determined by CRH testing, plays a part in the development of the metabolic syndrome.
    Metabolism 06/2004; 53(6):720-726. DOI:10.1016/S0026-0495(04)00078-2 · 3.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Emerging evidence implicates circadian abnormalities as a component of the pathophysiology of major depressive disorder (MDD). The suprachiasmatic nucleus (SCN) of the hypothalamus coordinates rhythms throughout the brain and body. On a cellular level, rhythms are generated by transcriptional, translational, and posttranslational feedback loops of core circadian genes and proteins. In patients with MDD, recent evidence suggests reduced amplitude of molecular rhythms in extra-SCN brain regions. We investigated whether unpredictable chronic mild stress (UCMS), an animal model that induces a depression-like physiological and behavioral phenotype, induces circadian disruptions similar to those seen with MDD. Activity and temperature rhythms were recorded in C57BL/6J mice before, during, and after exposure to UCMS, and brain tissue explants were collected from Period2 luciferase mice following UCMS to assess cellular rhythmicity. UCMS significantly decreased circadian amplitude of activity and body temperature in mice, similar to findings in MDD patients, and these changes directly correlated with depression-related behavior. While amplitude of molecular rhythms in the SCN was decreased following UCMS, surprisingly, rhythms in the nucleus accumbens (NAc) were amplified with no changes seen in the prefrontal cortex or amygdala. These molecular rhythm changes in the SCN and the NAc also directly correlated with mood-related behavior. These studies found that circadian rhythm abnormalities directly correlate with depression-related behavior following UCMS and suggest a desynchronization of rhythms in the brain with an independent enhancement of rhythms in the NAc. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
    Biological Psychiatry 02/2015; DOI:10.1016/j.biopsych.2015.01.011 · 9.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Depression is a chronic, recurrent and long-term disorder characterized by high rates of impairment and several comorbidities. Early life stress (ELS) is associated with the increased risk fordeveloping depression in adulthood, influencesits clinical course and predicts a poorer treatment outcome. Stressful life events play an important role in the pathogenesis of depression, being well established as acute triggers of psychiatric illness. The vulnerability for developing depression is associated to changes in neurobiological systems related to stress regulation. The hypothalamic-pituitary-adrenal (HPA) axisrespondsto external and internal stimuli. Reported results indicate that stress in early phases of development can induce persistent changes in the responseof the HPA axis to stress in adulthood, leading to a raised susceptibility to depression. These abnormalities appear to be related to the HPA axis deregulation in depression, partially due to an imbalance between glucocorticoid receptors (GR) andmineralocorticoid receptors(MR). While most studies have consistently demonstrated GR function is impaired in major depression (reduced GR-mediated feedback in HPA axis), data about the MR rolein depression are still limited and controversial. Thus, in this review article we summarizethe main reported findings about the consequencesofELS in HPA axis functioning and in the responsivityof MR/GR receptors in depression.
    Current Pharmaceutical Design 01/2015; 21. DOI:10.2174/1381612821666150105125500 · 3.29 Impact Factor