ACTH and multisteroid responses to corticotropin-releasing factor in depressive illness: Relationship to multisteroid responses after ACTH stimulation and dexamethasone suppression☆

Holsboer, Florian; Müller, Otto; Doerr, H. G.; Sippell, Wolfgang G.; Stalla, G. K.; Gerken, A.; Steiger, Axel; Boll, Erwin; Benkert, Otto

doi:10.1016/0306-4530(84)90034-9

Cited by 116 publications

(23 citation statements)

References 32 publications

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“…The blood samples were analysed as previously described (12). At each sampling time blood was drawn into heparinized tubes and immediately centrifuged at 4 * C before storage at -25 C. We employed a commercially available RIA (Gammacoat, Travenol) for determination of plasma cortisol levels.…”

Section: Analyticul Methodsmentioning

confidence: 99%

“…Elucidation of pathology underlying LHPA dysregulation in affective disorders was facilitated after ovine and hCRH were sequenced and made available for clinical research (8, 9). Studies applying this key hormone for LHPA regulation to depressives suggested a suprapituitary mechanism driving excessive ACTH and cortisol secretion, because hypersecretion of cortisol was associated with blunted ACTH response to CRH probes in these patients (10)(11)(12)(13)(14)(15). This finding proved to be unspecific for depression, because patients with other psychiatric disorders associated with altered LHPA function such as alcoholism (16,17), panic disorder (18, 19) and anorexia nervosa (20, 21) also responded with decreased ACTH to CRH challenge.…”

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confidence: 99%

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Cortisol Response to a Combined Dexamethasone‐Human Corticotrophin‐Releasing Hormone Challenge in Patients with Depression

Bardeleben

Holsboer

1989

J Neuroendocrinology

156

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We administered a combined dexamethasone-human corticotrophin-releasing hormone (hCRH) challenge test to 14 in-patients with a major depressive episode and to 14 age-matched controls. After pretreatment with 1.5 mg dexamethasone at 2300 h the day before, 100 pg hCRH was administered iv at 1500 h. Blood samples for cortisol determinations by radioimmunoassay were drawn at 1400 h, 1430 h and 1500 h before infusion of hCRH and thereafter every 15 min until 1700 h. Cortisol secretion after injection of hCRH assessed as area under the curve was significantly increased in patients with depression when compared to controls (14.5f4.3 ng x min x 1,00O/ml vs 3.1 k2.4 ng x min x 1,00O/ml). Multiple regression analysis among patients revealed a significant impact of age and severity of depression upon hCRH-induced cortisol secretion, whereas in normal controls no significant influence of age on cortisol secretion after hCRH emerged.Our data show that in depressed patients hCRH evokes an escape from dexamethasone-induced suppression of the pituitaryadrenocortical activity, whereas it fails to do so among controls. This finding suggests that at the pituitary level the action of hCRH is enhanced by a factor that is less sensitive to dexamethasone suppression in depression. We postulate that this factor is vasopressin.Dysregulation of the limbic-hypothalamic-pituitary-adrenocortical (LHPA) axis as measured by an increased number of adrenocorticotrophin (ACTH) bursts, elevated amount of cortisol released per secretory burst, resistance of cortisol to the suppressive action of dexamethasone, and blunted ACTH response after human corticotrophin-releasing hormone (hCRH) are among the major findings in depression research (1). Although the initially propagated diagnostic specificity of the dexamethasone suppression test (DST) for the subgroup of endogenous depression (2) did not receive full acceptance (3,4), the DST has been established as a method of monitoring clinical treatment (5-7). Elucidation of pathology underlying LHPA dysregulation in affective disorders was facilitated after ovine and hCRH were sequenced and made available for clinical research (8, 9). Studies applying this key hormone for LHPA regulation to depressives suggested a suprapituitary mechanism driving excessive ACTH and cortisol secretion, because hypersecretion of cortisol was associated with blunted ACTH response to CRH probes in these patients (10)(11)(12)(13)(14)(15). This finding proved to be unspecific for depression, because patients with other psychiatric disorders associated with altered LHPA function such as alcoholism (16, 17), panic disorder (18, 19) and anorexia nervosa (20, 21) also responded with decreased ACTH to CRH challenge.In male controls pretreated with dexamethasone, hCRH failed to induce an escape of plasma ACTH and cortisol from suppression, which led us to speculate that endogenous hypersecretion of CRH alone might not explain DST nonsuppression among a subgroup of depressives (22). In a sample of four depressed patients, we...

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Section: Analyticul Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Cortisol Response to a Combined Dexamethasone‐Human Corticotrophin‐Releasing Hormone Challenge in Patients with Depression

Bardeleben

Holsboer

1989

J Neuroendocrinology

156

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“…[4][5][6] There is a long body of evidence indicating disruption of hypothalamicpituitary-adrenal (HPA) axis function in depression, including the following key observations: increased 24-h elevations in cortisol production, 7 lack of suppression of plasma cortisol levels by dexamethasone, 8 increased concentrations of CRH in cerebrospinal fluid, 9 dysregulation of HPA responses to exogenous CRH administration [10][11][12] and loss of the negative correlation between plasma cortisol and continuously collected CSF CRH. 13 Of particular relevance, it has been demonstrated that antidepressants of various classes suppress CRH gene expression [14][15][16] in rodents and HPA activity in depressed 17 and healthy humans.…”

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confidence: 99%

Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans

et al. 2004

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There are well-replicated, independent lines of evidence supporting a role for corticotropinreleasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CRHR1 genotypes with the phenotype of antidepressant treatment response in 80 depressed Mexican-Americans in Los Angeles who completed a prospective randomized, placebo lead-in, double-blind treatment of fluoxetine or desipramine, with active treatment for 8 weeks. Subjects were included into the study if they had a diagnosis of depression without other confounding medical or psychiatric diagnoses or treatments. All patients were followed weekly and assessed for changes in the Hamilton rating scales for anxiety (HAM-A) and depression (HAM-D). Inclusion criteria in the study included a HAM-D of 18 or higher. Because CRHR1 affects both depression and anxiety. Patients were classified into a high-anxiety (HA) group if their HAM-A score was 18 or higher and in a low-anxiety (LA) group if their HAM-A score was less than 18. Utilizing the haplotype-tag single-nucleotide polymorphisms rs1876828, rs242939 and rs242941, we tested for haplotypic association between CRHR1 and 8-week response to daily antidepressant treatment. In the HA group (n ¼ 54), homozygosity for the GAG haplotype was associated with a relative 70% greater reduction in HAM-A scores compared to heterozygous (63.174.5 vs 37.176.9%, respectively, P ¼ 0.002). For HAM-D, GAG haplotype homozygosity was associated with a 31% greater reduction in scores after treatment compared to heterozygous (67.374.3 vs 51.276.0%, respectively, P ¼ 0.03). In those with loweranxiety levels at screening, there were no associations between CRHR1 genotype and percent change in HAM-A or HAM-D. These findings of increased response to antidepressants in highly anxious patients homozygous for the GAG haplotype of CRHR1 need to be independently validated and replicated. Such work would support the hypotheses that response to antidepressant treatment is heterogeneous and that the CRHR1 gene and possibly other genes in stress-inflammatory pathways are involved in response to antidepressant treatment. These findings also suggest that variations in the CRHR1 gene may affect response to CRHR1 agonists or antagonists. All data are deposited in www.pharmgkb. Keywords: corticotropin-releasing hormone; corticotropin-releasing hormone receptor; MexicanAmerican; Hispanic; depression; anxiety Major depression is a common and complex disorder of gene-environment interactions. 1 The specific genetic substrates and precipitating environmental factors have not yet been elucidated. The disorder affects 10% of males and 20% of females and has a point prevalence of 3%. Its cost to the US economy exceeds 100 billion dollars per year. 2 Over 20 drugs are approved by the US Food and Drug Administration for treatment of depression, each one with efficacy of approximately 60%. Various subgroups ...

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“…Some authors have found that patients with major depression exhibit a disturbed MHPG excretion (11)(12). An abnormal DST is an index for hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity (13)(14)(15)(16). MHPG in plasma and urine constitute an index of the general production rate of noradrenaline (17)(18)(19) and reflects sympathetic nervous system activity (20).…”

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confidence: 99%

Cortisol response to dexamethasone and noradrenergic function in depression

Maes

Ruyter

Suy

1987

Acta Psychiatr Scand

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Positive correlations between measures of hypothalamic-pituitary-adrenal (HPA)-axis activity and noradrenergic turnover have been reported in depression. To investigate this relationship the authors measured peak postdexamethasone cortisol levels (8 a.m., 4 p.m. and 11 p.m.) and the 24-hour urinary 3-methoxy-4-hydroxy-phenylglycol (MHPG) flow in 84 depressed patients. The results show that there is no positive association between those measures of HPA-axis and noradrenergic activity. On the contrary, patients with severe non-suppression (greater than or equal to 10 micrograms/dl or 277 nmol/l) tended to have a lower MHPG-excretion.

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ACTH and multisteroid responses to corticotropin-releasing factor in depressive illness: Relationship to multisteroid responses after ACTH stimulation and dexamethasone suppression☆

Cited by 116 publications

References 32 publications

Cortisol Response to a Combined Dexamethasone‐Human Corticotrophin‐Releasing Hormone Challenge in Patients with Depression

Cortisol Response to a Combined Dexamethasone‐Human Corticotrophin‐Releasing Hormone Challenge in Patients with Depression

Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans

Cortisol response to dexamethasone and noradrenergic function in depression

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