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.

  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Corticosterone is synthesized in the adrenal glands and is circulated throughout the body to perform regulatory functions in various tissues. The testis is known to synthesize and secrete testosterone and other androgens. We developed an accurate method to measure steroid content using liquid chromatography-mass spectrometry analysis. In the present study, significant levels of the precursor compounds of testosterone and corticosterone synthesis could be detected in rat testis using this method. After adrenalectomy, corticosterone remained in the blood and testicular tissue at approximately 1% of the amount present in the control testis. When the excised testicular tissue was washed and incubated with NADH, NADPH and progesterone, not only testosterone and its precursors but also 11-deoxycorticosterone and corticosterone were produced; the levels of 11-deoxycorticosterone and corticosterone increased with incubation time. The production rate of 11-deoxycorticosterone from progesterone was estimated to be approximately 1/20 that of 17-hydroxyprogesterone, and the corticosterone level was approximately 1/10 that of testosterone. These ratios coincided with those in the testicular tissue of the adrenalectomized rats, indicating that corticosterone was synthesized in the testis and not in the blood. A primary finding of this study was that corticosterone and testosterone were synthesized in a 1/10-20 ratio in the testis. It is concluded that corticosterone, which has various functions, such as the regulation of glycolysis and mediating spermatogenesis, is produced locally in the testis and that this the local production is convenient and functional to respond to local needs.
    PLoS ONE 02/2015; 10(2):e0117795. DOI:10.1371/journal.pone.0117795 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular disorders are a major cause of morbidity and mortality worldwide. Depression has been suggested as a risk factor for the development of cardiovascular disorders. This narrative review takes a look at the evidence linking the presence of depression and occurrence of cardiovascular disorders. The biological and behavioral mechanisms of this association are explored. The mechanisms proposed to explain the relationship between depression and cardiovascular disorders include abnormalities in hypothalamic-pituitary adrenal (HPA) axis, inflammatory cytokines, autonomic dysfunction, platelet abnormalities, and presence of behavioral risk factors like poor medication adherence, substance use and lack of exercise. The review also explores the treatment options for patients with depression who have risk factors for the development of cardiovascular disorders. Finally, the unique aspects of this association in the Indian context are discussed.
    03/2015; DOI:10.1016/j.jicc.2015.02.004


Available from