Neuroendocrine aspects of primary endogenous depression III. Cortisol secretion in relation to diagnosis and symptom patterns

Rubín, Robert T.; Poland, Russell E.; Lesser, Ira M.; Martin, David; Blodgett, A. L. Nelson; Winston, Robert A.

doi:10.1017/s003329170002585x

Cited by 56 publications

(21 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the lack of specificity of DST nonsuppression and the possible roles of age, anxiety and gender (Greden et al 1986;Rubin et al 1987a) do not allow use of this test alone to identify a clinically consistent subtype of major depression. Rather, recent data indicate that DST non-suppression may delineate a relevant biological subgroup only among inpatients with major depression (Coryell et al 2006; Table I.…”

Section: Alterations Of the Hpa Axis In Major Depressionmentioning

confidence: 99%

HPA axis and sleep: Identifying subtypes of major depression

Antonijevic

2008

Stress

View full text Add to dashboard Cite

It is increasingly acknowledged that the diagnosis of major depression encompasses patients who do not necessarily share the same disease biology. Though the diagnostic criteria allow the specification of different subtypes, e.g. melancholic and atypical features, a consensus still has to be reached with regard to the clinical symptoms that clearly delineate these subtypes. Beside clinical characteristics, biological markers may help to further improve identification of biologically distinct endophenotypes and, ultimately, to devise more specific treatment strategies. Alterations of the hypothalamus-pituitary-adrenal (HPA) axis and sleep architecture are not only commonly observed in patients with major depression, but the nature and extent of these alterations can help to identify distinct subtypes. Thus, a HPA overdrive, due to enhanced secretion of corticotropin-releasing hormone (CRH) and an impaired negative feedback via glucocorticoid receptors, seems to be most consistently observed in patients with melancholic features. These patients also show the clearest sleep-electroencephalogram (EEG) alterations, including disrupted sleep, low amounts of slow wave sleep (SWS), a short rapid eye movement (REM) latency and a high REM density. In contrast, patients with atypical features are characterized by reduced activity of the HPA axis and ascending noradrenergic neurons in the locus coeruleus. Though sleep-EEG alterations have been less thoroughly examined in these patients, there are data to suggest that SWS is not reduced and that REM sleep parameters are not consistently altered. While the atypical and melancholic subtypes of major depression may represent the extremes of a spectrum, the distinct clinical features provide an opportunity to further explore biological markers, as well as environmental factors, contributing to these clinical phenotypes. Moreover, dysregulations of the HPA axis and sleep-EEG alterations can also be induced in rodents, thereby allowing alignment of critical biological aspects of a human disease subtype with an animal model. Such "Translational Research" efforts should help to develop targeted therapies for distinct patient populations.

show abstract

Section: Alterations Of the Hpa Axis In Major Depressionmentioning

confidence: 99%

HPA axis and sleep: Identifying subtypes of major depression

Antonijevic

2008

Stress

View full text Add to dashboard Cite

show abstract

“…Patients suffering from major depression typically show increased circulating cortisol levels (Linkowski et al, 1985;Rubin et al, 1987;Deuschle et al, 1997), inadequate suppression of cortisol by dexamethasone (Carroll et al, 1968;Rubin et al, 1987), blunted adrenocorticotropic hormone (ACTH) responses to a corticotropin-releasing hormone (CRH) challenge (Holsboer et al, 1984;Gold et al, 1986), and exaggerated ACTH and cortisol responses to CRH after low-dose dexamethasone pretreatment (Heuser et al, 1994). These changes in hormonal responses may be the result of CRHproducing neurons in the hypothalamic paraventricular nucleus (PVN) (Owens and Nemeroff, 1991;Chrousos and Gold, 1992;Holsboer et al, 1994).…”

Section: Abstract: Corticotropin-releasing Hormone (Crh); Glucocortimentioning

confidence: 99%

Reduced Activity of Hypothalamic Corticotropin-Releasing Hormone Neurons in Transgenic Mice with Impaired Glucocorticoid Receptor Function

et al. 1998

View full text Add to dashboard Cite

Loss of central glucocorticoid receptor (GR) function is thought to be involved in the development of neuroendocrine and psychiatric disorders associated with corticotropin-releasing hormone (CRH) hyperactivity. The possible causal relationship between defective GR function and altered activity of CRH neurons was studied in transgenic mice (TG) expressing antisense RNA against GR. Immunocytochemical studies showed significant reductions in CRH immunoreactive neurons in the paraventricular nucleus (PVN) and in CRH and vasopressin (AVP) stores in the external zone of the median eminence. Concomitantly, stimulus-evoked CRH secretion from mediobasal hypothalami of TG mice in vitro was reduced significantly. However, CRH mRNA levels in the PVN of TG mice were marginally lower than those in wild-type (WT) mice.125 I-CRH binding autoradiography revealed no differences between WT and TG animals in any of the brain regions that were studied. Basal plasma corticosterone (cort) levels and 125 I-CRH binding, CRH-R 1 mRNA, POMC mRNA, and POMC hnRNA levels in the anterior pituitary gland were similar in WT and TG mice. Intraperitoneal injection of interleukin-1␤ (IL-1␤) increased plasma cort levels, CRH mRNA in the PVN, and anterior pituitary POMC hnRNA similarly in WT and TG mice. The injection of saline significantly reduced anterior pituitary CRH-R 1 mRNA levels in WT mice, but not in TG mice, whereas IL-1␤ produced a decrease in these mRNA levels in both strains.The data show that long-term GR dysfunction can be associated with reduced activity of CRH neurons in the PVN and decreased sensitivity of pituitary CRH-R 1 mRNA to stimulusinduced downregulation. Moreover, the hypothalamic changes observed in this model suggest that impaired GR function, at least if present since early embryonic life, does not necessarily result in CRH hyperexpression characteristics of disorders such as major depression.

show abstract

“…Major depression is associated with increased cortisol secretion, as demonstrated by a number of investigators (Sachar et al, 1973;Halbreich et al, 1985;Pfohl et al, 1985;Linkowski et al, 1985;Rubin et al, 1987;Young et al, 2001). However, it is still unclear if this increased cortisol secretion is a function of increased ACTH drive from the hypothalamus or is a result of increased adrenal response to ACTH.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in ACTH pulsatility following metyrapone blockade in patients with major depression

Young¹,

Ribeiro²,

Ye³

2007

Psychoneuroendocrinology

View full text Add to dashboard Cite

SummaryNumerous studies suggest that increased central drive to the hypothalamic-pituitary adrenal axis occurs in patients with major depression. To determine if increased central drive occurs throughout the 24H, we evaluated ACTH secretion under metyrapone blockade of cortisol production. We collected blood every 10 minutes for measurement of ACTH and data were analyzed for ACTH pulsatility using the pulse detection algorithm deconvolution. We studied 28 patients with major depression and 28 age and sex matched control subjects, of which 9 pairs were men and 19 pairs were women. We found a significant group by sex interaction with number of ACTH pulses (p=.04); depressed men showed more ACTH pulses over 24H than matched control men (p=0.02). There was also a significant sex difference in AUC pulses with men showing a smaller AUC ACTH than women. Previous analyses of these data with RM-ANOVA showed a smaller ACTH response in depressed men compared to control men. These data suggest that pulsatility and mean ACTH levels are examining different aspects of HPA axis function, and that the types of HPA axis dysregulation in depression may differ between men and women.

show abstract

Neuroendocrine aspects of primary endogenous depression III. Cortisol secretion in relation to diagnosis and symptom patterns

Cited by 56 publications

References 61 publications

HPA axis and sleep: Identifying subtypes of major depression

HPA axis and sleep: Identifying subtypes of major depression

Reduced Activity of Hypothalamic Corticotropin-Releasing Hormone Neurons in Transgenic Mice with Impaired Glucocorticoid Receptor Function

Sex differences in ACTH pulsatility following metyrapone blockade in patients with major depression

Contact Info

Product

Resources

About