Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression

Zobel, Astrid; Nickel, Thomas; Sonntag, Annette; Uhr, Manfred; Holsboer, Florian; Ising, Marcus

doi:10.1016/s0022-3956(01)00013-9

Cited by 336 publications

(224 citation statements)

References 31 publications

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“…This, however, is indicative of a generally enhanced adrenal sensitivity to ACTH in female rats under these conditions. Consistent with these findings, it could also be demonstrated in human studies that gender profoundly affects DEX/CRH test outcome (Heuser et al 1994;Zobel et al 2001). …”

Section: Aberrant Outcome Of the Combined Dex/crh Test In Male Hab Ratssupporting

confidence: 67%

Vasopressin Mediates the Response of the Combined Dexamethasone/CRH Test in Hyper-anxious Rats Implications for Pathogenesis of Affective Disorders

Keck

Wigger

Welt

et al. 2002

Neuropsychopharmacology

158

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To investigate the neuroendocrine alterations linked to inborn emotionality in two Wistar rat lines selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, we administered the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH)testNeuroendocrine studies provide strong indications that hyperactivity of central corticotropin-releasing hormone (CRH) circuits, resulting in a characteristic dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, plays a causal role in the symptomatology of affective and anxiety disorders (review: Keck and Holsboer 2001). The effects of CRH are modulated by vasopressin (AVP), which, after prolonged stress and in senescence, is increasingly coexpressed and secreted from hypothalamic CRH neurons in both humans and rodents (Antoni 1993;Tilders et al. 1993;Hatzinger et al. 2000;Keck et al. 2000). Similarly, increased numbers of CRH neurons that coexpress AVP mRNA have been found in the hypothalamus of depressed patients (Raadsheer et al. 1993;Purba et al. 1996). The excessive release of CRH and AVP into hypophysial portal blood is thought to increase the secretion of corticotropin (ACTH) from pituitary corticotrope cells, and this in turn to increase the release of corticosteroids from the adrenal gland. In this context, a variety of changes in HPA system regulation have been demonstrated in psychiatric disorders such as major depression, among them defective negative feedback of the HPA system, basal hypercortisolemia, inappropriate HPA suppression by the synthetic corticosteroid dexamethasone (DEX) and a paradoxical stimulation of ACTH secretion by CRH after DEX pretreatment (review: Holsboer and Barden 1996;Holsboer 2000). In depression, the combined DEX/CRH test, in which DEX-pretreated subjects receive a single dose of CRH, has proven to be the most sensitive tool for the detection of altered HPA regulation. Depending on age and gender, up to 90% of patients with depression show this neuroendocrine phenomenon (Heuser et al. 1994). Moreover, studies using the DEX/CRH test not only agree that normalization of an initial aberrance is predictive of a favorable treatment response but also corroborate other evidence that a persistent HPA abnormality correlates with chronicity or relapse (Heuser et al. 1996;Zobel et al. 1999). Since activation of corticosteroid receptors suppresses the synthesis and release of CRH and AVP from the hypothalamic paraventricular nucleus (PVN) , these findings are consistent with the hypothesis of functionally impaired corticosteroid receptor signaling in both depressed patients (Modell et al. 1997) and healthy subjects at genetic risk for depression Modell et al. 1998).As the mechanisms underlying the abnormal HPA reactivity in patients with certain psychiatric disorders are not fully understood, animal models are needed to further investigate the hypothesized linkage between these disorders and changes in the regulation of the HPA system. After several generations of selective breeding, we could establish ...

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Section: Aberrant Outcome Of the Combined Dex/crh Test In Male Hab Ratssupporting

confidence: 67%

Vasopressin Mediates the Response of the Combined Dexamethasone/CRH Test in Hyper-anxious Rats Implications for Pathogenesis of Affective Disorders

Keck

Wigger

Welt

et al. 2002

Neuropsychopharmacology

158

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“…Given that the ability of antidepressants to regulate the HPA axis is tightly coupled to their clinical efficacy (Holsboer and Barden, 1996;Greden et al, 1983;Ribeiro et al, 1993;Zobel et al, 2001), these data suggest that upregulation of the endocannabinoid system is involved in the normalization of hypercortisolemia that accompanies remission of depression. These data also support the suggestion that the endocannabinoid system could serve as a suitable target for the development of novel antidepressants (Hill and Gorzalka, 2005a;Jiang et al, 2005;Gobbi et al, 2005), especially for melancholic depression , which exhibits a preferential response to tricyclic antidepressants and reliably exhibits hyperactivity of the HPA axis (Rush and Weissenburger, 1994;Bielski and Friedel, 1976;Gold and Chrousos, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…The ability of antidepressants to suppress HPA axis hyperactivity has been shown to be coupled to their clinical efficacy (Appelhof et al, 2006;Young et al, 2004). Specifically, normalization of glucocorticoid feedback and hypersecretion is associated with clinical remission, and patients who do not exhibit normalization of this system exhibit a significantly higher tendency to experience depressive relapse and have a poorer long-term prognosis (Ribeiro et al, 1993;Greden et al, 1983;Zobel et al, 2001). These data demonstrate that the ability of antidepressants to regulate the HPA axis could be integral to the remission of depressive symptoms; however, the mechanism by which antidepressants exert this effect is currently not well understood.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

Hill

Sinopoli

et al. 2006

Neuropsychopharmacol

110

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The efficacy of antidepressants has been linked in part to their ability to reduce activity of the hypothalamic-pituitary-adrenal (HPA) axis; however, the mechanism by which antidepressants regulate the HPA axis is largely unknown. Given that recent research has demonstrated that endocannabinoids can regulate the HPA axis and exhibit antidepressant potential, we examined the hypothesis that the endocannabinoid system is regulated by long-term antidepressant treatment. Three-week administration of the tricyclic antidepressant desipramine (10 mg/kg/day) resulted in a significant increase in the density of the cannabinoid CB 1 receptor in the hippocampus and hypothalamus, without significantly altering endocannabinoid content in any brain structure examined. Furthermore, chronic desipramine treatment resulted in a reduction in both secretion of corticosterone and the induction of the immediate early gene c-fos in the medial dorsal parvocellular region of the paraventricular nucleus of the hypothalamus (PVN) following a 5 min exposure to swim stress. Acute treatment with the CB 1 receptor antagonist, AM251 (1 mg/kg), before exposure to swim stress, completely occluded the ability of desipramine to reduce both corticosterone secretion and induction of c-fos expression in the PVN. Collectively, these data demonstrate that CB 1 receptor density in the hippocampus and hypothalamus is increased by chronic tricyclic antidepressant treatment, and suggest that this upregulation could contribute to the ability of tricyclic antidepressants to suppress stress-induced activation of the HPA axis.

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“…CYP3A4 inducing drugs like barbiturates and carbamazepine accelerate dexamethasone metabolization, which leads to higher ACTH and cortisol responses to CRH stimulation in the combined DEX/CRH test (von Bardeleben et al 1988;Zobel et al 2001). Contrary to carbamazepine, lithium is not known Figure 2.…”

Section: Discussionmentioning

confidence: 99%

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Bschor

Adli

Baethge

et al. 2002

Neuropsychopharmacology

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Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressantwere assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P . M . and CRH stimulation at 3 P . M . on the next day). Twenty-four patients were reassessed after response was determined or, in cases of nonresponse, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton DepressionRating Scale Regardless of the initial choice of antidepressant, about 30 to 40% of patients with major depressive disorder will not respond sufficiently (Thase and Rush 1995 Among the various treatment options that have been proposed for non-responding depressed patients, lithium augmentation has been recommended as a first-line strategy . The efficacy of lithium augmentation has been well documented in placebo-controlled acute (Joffe et al. 1993;Katona et al. 1995;Baumann et al. 1996) and continuation treatment trials (Bauer et al. 2000;Bschor et al. 2002) using different classes of antidepressants. A recent meta-analysis confirmed the evidence that lithium augmentation is superior to placebo augmentation for the treatment of unipolar major depression, with a median response rate of 50% across double-blind studies (Bauer and Döpfmer 1999). Severity of depression was recently identified as a clinical predictor of response to lithium augmentation (Bschor et al. 2001). Better knowledge of the neurobiological mechanisms of lithium augmentation would help to identify patients who will respond favorably to this treatment intervention. However, to date, the mode of action of lithium augmentation is unknown. Shortly after the initial report on its efficacy (de Montigny et al. 1981), it was postulated by de Montigny et al. (1983) that a pharmacodynamic action mediated via the serotonergic systems might account for the synergistic effect of lithium when added to a tricyclic antidepressant.Another system potentially involved in its mechanism of action is the hypothalamic-pituitary-adrenocortical (HPA) system, putatively the best studied biological system in affective disorders (Dinan 1997). The most sensitive challenge test of the HPA system is the combined dexamethasone/CRH test (DEX/CRH test) (Heuser 1998). A dysfunction in the regulation of the HPA system, especially an overstimulation of ACTH and cortisol in the DEX/CRH test, was repeatedly shown in depressed patients (for a review see Steckler et al. 1999;Holsboer 2000). In treatment studies with ...

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Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression

Cited by 336 publications

References 31 publications

Vasopressin Mediates the Response of the Combined Dexamethasone/CRH Test in Hyper-anxious Rats Implications for Pathogenesis of Affective Disorders

Vasopressin Mediates the Response of the Combined Dexamethasone/CRH Test in Hyper-anxious Rats Implications for Pathogenesis of Affective Disorders

Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

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