Combined Dexamethasone Suppression-Corticotropin-Releasing Hormone Stimulation Test in Studies of Depression, Alcoholism, and Suicidal Behavior

Division of Neuroscience, Department of Psychiatry, Columbia University, New York, USA.
The Scientific World Journal (Impact Factor: 1.73). 02/2006; 6:1398-404. DOI: 10.1100/tsw.2006.251
Source: PubMed

ABSTRACT The hypothalamic-pituitary-adrenal (HPA) axis controls the secretion of corticotropin-releasing hormone (CRH), corticotropin (adrenocorticotropic hormone, ACTH), and cortisol. The dexamethasone suppression test (DST) is the most frequently used test to assess HPA system function in psychiatric disorders. Patients who have failed to suppress plasma cortisol secretion, i.e., who escape from the suppressive effect of dexamethasone, have a blunted glucocorticoid receptor response. After CRH became available for clinical studies, the DST was combined with CRH administration. The resulting combined dexamethasone suppression-corticotropin-releasing hormone stimulation (DST-CRH) test proved to be more sensitive in detecting HPA system changes than the DST. There is a growing interest in the use of the DEX-CRH test for psychiatric research. The DEX-CRH test has been used to study different psychiatric conditions. Major depression, alcoholism, and suicidal behavior are public health problems around the world. Considerable evidence suggests that HPA dysregulation is involved in the pathogenesis of depressive disorders, alcoholism, and suicidal behavior. Over the past 2 decades, there has been a shift from viewing excessive HPA activity in depression as an epiphenomenon to its having specific effects on symptom formation and cognition. The study of HPA function in depression, alcoholism, and suicidal behavior may yield new understanding of the pathophysiology of these conditions, and suggest new approaches for therapeutic interventions. The combined DEX-CRH test may become a useful neuroendocrinological tool for evaluating psychiatric patients.

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    • "The most frequently utilized test to assess HPA system function in psychiatric disorders is the dexamethasone suppression test (DST) (Sher, 2006). The DST is performed by measuring cortisol levels following administration of a low dose of dexamethasone , normally suppressing cortisol through the negative feedback inhibition of the HPA axis. "
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    ABSTRACT: OBJECTIVES: The dexamethasone/corticotropin-releasing hormone (DEX/CRH) test has been proposed as a potential diagnostic test for major depressive disorder (MDD). A previously proposed four-step approach assesses the stage of development for a biological finding into a clinically useful diagnostic test. Using this approach, we evaluated the progress of DEX/CRH test using meta-analysis as part of the step-1. METHODS: A literature review identified 15 studies of DEX/CRH test in patients with MDD and healthy controls. Meta-analysis estimated the effect size, heterogeneity, and confidence intervals using random effects models. Studies consistent with any step of the four-step approach were identified, and their characteristics were presented. RESULTS: Eleven studies reported significantly higher cortisol levels with the DEX/CRH test in patients with MDD, compared to healthy controls. Eight eligible studies were included in meta-analysis, and had an effect size of 1.34 (95% confidence interval: 0.70-1.97). Most studies were step-1 studies (comparison of patients and healthy controls), and no step-4 studies (multicenter trials) were found. CONCLUSION: This review emphasizes that despite appearing as a promising test, the DEX/CRH has not been adequately studied for the required stages of development into a clinically useful laboratory test. Particularly, additional step-3 and step-4 studies are necessary.
    01/2013; 208(2). DOI:10.1016/j.psychres.2012.09.032
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    • "Watson et al. (2006) recently reported that the dexamethasone suppression/corticotrophinreleasing-hormone (dex/CRH) test (which involves administration of the DST and an additional CRH challenge test) had similar sensitivity but greater specificity (71.4% vs 47.6%) than the standard DST in differentiating healthy controls from a mixed sample of mood disorders patients. Such investigations have produced a great deal of early enthusiasm about the dex/CRH test by some researchers (e.g., Sher, 2006). The dex/CRH test may prove superior to the original DST on certain parameters, but similar problems with inadequately controlling for known confounds can be found in the dex/CRH literature to date. "
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    ABSTRACT: Previous research has shown that psychotic major depression (PMD) is often associated with higher rates of nonsuppression on the dexamethasone suppression test (DST) compared with nonpsychotic major depression (NMD), suggesting the potential importance of cortisol hypersecretion in the psychotic subtype of the disorder. However, these patient groups also are known to differ from one another on a variety of other clinical variables, and there are numerous factors independent of diagnostic status known to affect the DST. Thus, we investigated possible confounds that could help account for the apparent DST abnormalities in PMD sometimes reported in past research. Hospitalized patients with PMD (n = 11) and NMD (n = 58) were compared on the DST and other clinical variables. As expected, PMD patients showed significantly higher rates of DST nonsuppression (55% vs. 24%; p = 0.04). However, PMD patients also had significantly higher levels of anxiety severity (p = 0.01). The higher rates of nonsuppression in the PMD group were attenuated when these patients were compared with a subsample of NMD patients matched on anxiety severity (55% vs. 55%). Implications for future research on biological markers of PMD are discussed.
    The Journal of nervous and mental disease 07/2009; 197(6):395-400. DOI:10.1097/NMD.0b013e3181a775cf · 1.69 Impact Factor
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    • "Long lasting enhancement of cortisol plasma levels due to enhanced CRH release, which overrides the physiological negative feedback mechanisms, has been frequently correlated with depression and anxiety disorders (Sher, 2006). Indeed CRH has been investigated not only to regulate the activity of the HPA axis. "
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    ABSTRACT: Benzodiazepines are known to modulate the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis by antagonizing the effects of corticotropin-releasing factor (CRH). Besides regulating the HPA axis CRH evolves properties of a neurotransmitter in the limbic system that is closely involved in the delivery of the emotional consequences of the stress response. At a superordinated level Neuropeptide Y (NPY) and Cholecystokinin (CCK) affect the release of CRH and modulate thereby the intensity of the physiological stress response. Benzodiazepine treatment interferes not only with the release of CRH but also with the release of NPY and CCK. Alterations in the intracortical ratio of NPY, CCK and CRH are correlated with behavioural changes like increased respectively decreased anxiety and subsequent alterations in the activity of the HPA axis. Recent research offers the possibility that the alterations of plasma levels of these neuropeptides are not only a secondary phenomenon due to drug intake, but that low levels of those neuropeptides that modulate anxiety and fear can possibly explain addiction to substances that counterbalance these deficits. Depending on the available results possible implications of NPY and CCK on benzodiazepine addiction and withdrawal symptoms are reviewed, thereby providing topics for further research.
    Human Psychopharmacology Clinical and Experimental 04/2008; 23(3):171-81. DOI:10.1002/hup.911 · 2.19 Impact Factor
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