The combined DEX-CRH test in treatment course and long-term outcome of major depression

Hatzinger, Martin; Hemmeter, Ulrich; Baumann, K.; Brand, Serge; Holsboer‐Trachsler, Edith

doi:10.1016/s0022-3956(02)00021-3

Cited by 87 publications

(54 citation statements)

References 44 publications

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“…We could, however, observe a positive correlation of the ACTH and cortisol response with the number of previous episodes. Similar results were shown by Hatzinger et al (2002), who also found a positive correlation of the number of previous episodes with the cortisol response in the Dex-CRH test but not the overall duration of illness. Repetitive states of HPA-axis hyperactivity may by themselves alter the responsiveness of the stress-hormone system, by for example changing the DNA-methylation status in the promoter regions of glucocorticoid-responsive genes (Kagoshima et al, 2001;Thomassin et al, 2001).…”

Section: Factors Influencing the Dex-crh Testsupporting

confidence: 84%

“…Even though over 80% of depressed patients are reported to display an increased response in this test (Heuser et al, 1994b), cortisol and ACTH responses in acutely depressed patients actually show a broad range within (Heuser et al, 1994b) and between studies (mean peak cortisol value reported in Heuser et al (1994b) is about 200 ng/ml, while Zobel et al (2001), Hatzinger et al (2002), and Rybakowski and Twardowska (1999) report mean peak cortisol values from about 20 to 60 ng/ml). In our own sample, peak cortisol values range from 3.9 to 332.4 ng/ml (mean/ SD ¼ 62.6/55.3).…”

Section: Introductionmentioning

confidence: 81%

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Pharmacological and Nonpharmacological Factors Influencing Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test

Künzel

Binder

Nickel

et al. 2003

Neuropsychopharmacol

135

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The most consistent biological findings in patients with depression are abnormalities in the hypothalamic-pituitary-adrenal (HPA)-axis, which can be measured using the combined dexamethasone-suppression/CRH-stimulation (Dex-CRH) test. The reactivity of the HPAaxis in this test, however, ranges over several orders of magnitude in depressed patients with comparable severity of symptoms. In this present study, we investigate which factors influence the magnitude of the response in the Dex-CRH test in 235 acutely depressed inpatients. We first examined the effects of common confounders shown to influence the HPA-axis, such as caffeine and nicotine consumption, acute stressors during the test, weight, gender, and age. Of all these variables, only female sex and nicotine consumption were positively correlated with the cortisol or ACTH response, respectively. As for the effects of psychopharmacological treatment, only the intake of carbamazepine and the fact of having relapsed under an established pharmacotherapy significantly increased the response in the Dex-CRH test, whereas the presence or absence of antidepressant treatment, the type of antidepressant treatment, or the number of ineffective antidepressant treatment trials during the index episode up to admission did not have any effect. We also found a positive correlation of the number of previous episodes, the overall HAM-D score and the severity of somatic/vegetative symptoms with the results in the Dex-CRH test. These results underline that in depressed patients this test is not majorly influenced by disease-unrelated factors. In addition, current antidepressant treatment does not appear to affect test outcome in the absence of clinical response. The influence of the number of previous episodes and relapse under pharmacotherapy suggests that HPA-axis reactivity may be altered by repetitive states of hypercortisolemia or continuous antidepressant treatment. Finally, more severe vegetative symptoms are associated with an enhanced HPA-axis activity.

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Section: Factors Influencing the Dex-crh Testsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 81%

Pharmacological and Nonpharmacological Factors Influencing Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test

Künzel

Binder

Nickel

et al. 2003

Neuropsychopharmacol

135

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“…OC is associated with an elevated risk of depression (Dragano et al, 2008), and these two conditions, OC (Siegrist et al, 1990;Joksimovic et al, 1999;Kuper et al, 2002), and depression (Musselman et al, 1998;Parissis et al, 2007;Van der Kooy et al, 2007), were found to increase the risk of CHD. Both of these risk factors of CHD show elevated cortisol secretion in the combined dex/CRH test, suggesting an HPA system dysregulation (Zobel et al, 2001;Hatzinger et al, 2002;Ising et al, 2005). However, while we were unable to observe a correlation between ACTH secretion and OC levels, some, but not all, studies suggested elevated pituitary reactivity, as evidenced by increased ACTH release following CRH injection in the combined dex/CRH test with depression (Heuser et al, 1994;Schule et al, 2003).…”

Section: Discussioncontrasting

confidence: 64%

“…Results of the combined dex/CRH test demonstrate that depression and depressive symptoms are associated with elevations in hormonal responses, particularly of cortisol (Zobel et al, 2001;Hatzinger et al, 2002;Ising et al, 2005). Elevated hormonal responses to the dex/CRH test in depression have been proposed to reflect impaired glucocorticoid functioning, a key mechanism in the pathogenesis of depression (Ising et al, 2005) that might at least in part underlie the increased CHD risk with depression (Girod and Brotman, 2004;Lett et al, 2004;Parissis et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Higher overcommitment to work is associated with higher plasma cortisol but not ACTH responses in the combined dexamethasone/CRH test in apparently healthy men and women

Wirtz

Siegrist

Schuhmacher

et al. 2010

Psychoneuroendocrinology

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Higher overcommitment to work is associated with higher plasma cortisol but not ACTH responses in the combined dexamethasone/CRH test in apparently healthy men and women Wirtz, P H; Siegrist, J; Schuhmacher, A; Hoefels, S; Maier, W; Zobel, A W Wirtz, P H; Siegrist, J; Schuhmacher, A; Hoefels, S; Maier, W; Zobel, A W (2009). Higher overcommitment to work is associated with higher plasma cortisol but not ACTH responses in the combined dexamethasone/CRH test in apparently healthy men and women. Psychoneuroendocrinology:Epub ahead of print. Higher overcommitment to work is associated with higher plasma cortisol but not ACTH responses in the combined dexamethasone/CRH test in apparently healthy men and women Abstract BACKGROUND: Overcommitment (OC) is a pattern of excessive striving that has been associated with alterations in the hypothalamus-pituitary-adrenal (HPA) system. To investigate whether overcommitment is associated with alterations in HPA system function we measured cortisol and adrenocorticotropin (ACTH) release in response to the combined dexamethasone/CRH test. METHODS: We recruited 92 men and 108 women of a wide range of OC scores including the minimum (6) and maximum (24) of possible OC scores (mean+/-SEM: 13.25+/-.27). We repeatedly measured plasma cortisol and ACTH levels in the combined dexamethasone/CRH test after injection of 100mul CRH preceded by administration of 1.5mg dexamethasone the night before. Moreover, we assessed depressive symptoms (Beck Depression Inventory, BDI) and work stress (effort-reward-imbalance, ERI). RESULTS: Independent of age and gender, higher OC was associated with higher repeated cortisol (interaction time-by-OC: p=.014, f=.15) but not ACTH (p=.22) secretion in the combined dexamethasone/CRH test. Similarly, higher cortisol (beta=.16, p=.029, R(2)=.02) but not ACTH (p=.47) increase following CRH injection was predicted by higher OC. Depressive symptoms (BDI score) and work stress scores (effort-reward-ratio) did not relate to neuroendocrine responses to the dexamethasone/CRH test. Controlling for depressive symptoms and work stress scores in addition to age and gender did not change results. OC was not associated with ACTH or cortisol pre-test levels. DISCUSSION: Whereas OC was not associated with alterations in negative feedback sensitivity after dexamethasone administration, our findings indicate that with increasing OC scores, a higher reactivity of the adrenal cortex together with a normal reactivity of the pituitary is observed following subsequent stimulation by CRH injection. Discussion: Whereas OC was not associated with alterations in negative feedback sensitivity after dexamethasone administration, our findings indicate that with increasing OC scores, a higher reactivity of the adrenal cortex together with a normal reactivity of the pituitary is observed following subsequent stimulation by CRH injection. Higher overcommitment to work is associated with higher plasma cortisol but not ACTH responses in the combined dexamethasone/CRH test in apparently healthy ...

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“…In line with this, hormonal responses to the DEX/CRH test also restored after successful treatment with antidepressants (Holsboer-Trachsler et al, 1991;Heuser et al, 1996;Baghai et al, 2002;Hatzinger et al, 2002), suggesting that the DEX/CRH test is a useful statedependent marker. However, it has been argued that DEX/ CRH test results may be trait dependent, particularly in bipolar patients Schmider et al, 1995;Watson et al, 2004;Ising et al, 2005).…”

Section: Introductionmentioning

confidence: 75%

Assessment of the Dexamethasone/CRH Test as a State-Dependent Marker for Hypothalamic-Pituitary-Adrenal (HPA) Axis Abnormalities in Major Depressive Episode: A Multicenter Study

Kunugi

Ida

Owashi

et al. 2005

Neuropsychopharmacol

189

108

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There is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in depression. Growing evidence has suggested that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA axis abnormalities. We organized a multicenter study to assess the DEX/CRH test as a state-dependent marker for major depressive episode in the Japanese population. We conducted the DEX/CRH test in 61 inpatients with major depressive episode (Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)) and 57 healthy subjects. In all, 35 patients were repeatedly assessed with the DEX/CRH test on admission and before discharge. The possible relationships between clinical variables and the DEX/ CRH test were also examined. Significantly enhanced pituitary-adrenocortical responses to the DEX/CRH test were observed in patients on admission compared with controls. Such abnormalities in patients were significantly reduced after treatment, particularly in those who underwent electroconvulsive therapy (ECT) in addition to pharmacotherapy. Age and female gender were associated with enhanced hormonal responses to the DEX/CRH test. Severity of depression correlated with DEX/CRH test results, although this was explained, at least in part, by a positive correlation between age and severity in our patients. Medication per se was unrelated to DEX/CRH test results. These results suggest that the DEX/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities in major depressive episode during treatment. Restoration from HPA axis abnormalities occurred with clinical responses to treatment, particularly in depressed patients who underwent ECT.

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The combined DEX-CRH test in treatment course and long-term outcome of major depression

Cited by 87 publications

References 44 publications

Pharmacological and Nonpharmacological Factors Influencing Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test

Pharmacological and Nonpharmacological Factors Influencing Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test

Higher overcommitment to work is associated with higher plasma cortisol but not ACTH responses in the combined dexamethasone/CRH test in apparently healthy men and women

Assessment of the Dexamethasone/CRH Test as a State-Dependent Marker for Hypothalamic-Pituitary-Adrenal (HPA) Axis Abnormalities in Major Depressive Episode: A Multicenter Study

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