Differences in plasma ACTH and cortisol between depressed patients and normal controls

doi:10.1016/0006-3223(85)90004-6

Biological Psychiatry

Volume 20, Issue 10, October 1985, Pages 1055-1072

https://doi.org/10.1016/0006-3223(85)90004-6 Get rights and content

Abstract

Although studies have repeatedly demonstrated that depressed patients average higher baseline and postdexamethasone serum cortisol than normal controls, studies examining similar trends in adrenocorticotrophic hormone (ACTH) have produced conflicting results. The current study uniquely employs 48 hr of every 20-min serum sampling: the first 24 hr prior to dexamethasone administration and the second 24 hr subsequent. The depressed patients showed higher baseline cortisol levels than normal controls, with the greatest differences between 2 am and 6 am. After an 11 pm dose of dexamethasone, the difference was greatest between the hours of 8 am and 4 pm. Among the depressed patients, those who reported recent weight loss had significantly higher plasma ACTH and cortisol levels than those without weight loss. Depressed patients without weight loss had higher baseline plasma ACTH than normal controls, and the differences reached significance during some time periods.

References (31)

V.S. Fang et al.
Plasma ACTH and cortisol levels in depressed patients: Relation to dexamethasone suppression test
Life Sci
(1981)
F. Holsboer et al.
Cortisol, 11-deoxycortisol, and ACTH concentrations after dexamethasone in depressed patients and healthy volunteers
Psychiatry Res
(1984)
N.H. Kalin et al.
Plasma ACTH and cortisol concentrations before and after dexamethasone
Psychiatry Res
(1982)
D.A. Lewis et al.
The influence of age on the cortisol response to dexamethasone
Psychiatry Res
(1984)
H. Nasrallah et al.
Dexamethasone nonsuppression predicts the antidepressant effects of sleep deprivation
Psychiatry Res
(1982)
B.I. Yerevanian et al.
Plasma ACTH levels in primary depression: relationship to the 24-hour dexamethasone suppression test
Psychiatry Res
(1983)
B.I. Yerevanian et al.
The influence of weight loss on the Dexamethasone Suppression Test
Psychiatry Res
(1984)
American Psychiatric Association
DSM III: Diagnostic and Statistical Manual of Mental Disorders
M. Berger et al.
Influence of weight loss on the dexamethasone suppression test
Arch Gen Psychiatry
(1983)
B.J. Carroll et al.
Neuroendocrine regulation in affective disorders

B.J. Carroll et al.

A specific laboratory test for the diagnosis of melancholia

Arch Gen Psychiatry

(1981)

B.J. Carroll et al.

Neuroendocrine regulation in affective disorders

S.C. Dilsaver et al.

Antidepressant withdrawal and hypothalamic-pituitary-adrenal regulation

C.K. Edelstein et al.

Effects of weight loss on the Dexamethasone Suppression Test

Am J Psychiatry

(1983)

H.L. Fehm et al.

Paradoxical ACTH response to glucocorticoids in Cushing's disease

N Engl J Med

(1977)

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Clinical observations indicate that diverse disorders disrupt hypothalamic-corticotropic-adrenal (HPA) homeostasis. Prominent examples include depression, mania, dementia, posttraumatic stress disorder, chronic fatigue syndrome, alcoholism, visceral adiposity, diabetes mellitus, polycystic ovarian disease, acute illness, systemic disease, and multiorgan failure.1–19 Age, gender, and sex steroids are salient physiologic factors that determine the magnitude and duration of stress-adaptive cortisol production, albeit via mechanisms that are essentially unknown in the human.20–34
Clinical utility of serum biomarkers for major psychiatric disorders
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In major depression, there are long-standing observations of alterations in HPA axis function (Holsboer and Barden, 1996; Nemeroff and Vale, 2005). Evidence for hyperactivity of the HPA-axis was shown by higher daytime cortisol levels, nonsuppression after dexamethasone ingestion and higher corticotropin-releasing hormone, and adrenocorticotropin hormone levels among persons with depression (Carroll et al., 1976; Gold et al., 1995; Pfohl et al., 1985; Stokes et al., 1984), and recently confirmed by Vreeburg et al. (2009). However, inconsistencies are present in these studies, which most likely results from the heterogeneity of the depression syndrome.
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Depression is associated with dysregulated hypothalamic–pituitary–adrenal (HPA) axis function, overactivity of the sympathoadrenal system, and increased levels of inflammation markers. It is not known whether these biological processes are disproportionately elevated in response to acute negative emotional arousal by mental stress (MS). The present study investigates responses of neurohormones and inflammatory markers to MS in 14 clinically depressed (age: 42 ± 10 years; 50% female) and 14 non-depressed control (age: 39 ± 6 years; 50% female) participants. Heightened acute MS reactivity was documented in depressed participants (adrenocorticotropic hormone, ρ = 0.001; norepinephrine, ρ = 0.042; epinephrine, ρ = 0.039), and a delayed increase in cortisol was observed (ρ = 0.002). Inflammation markers increased more strongly in depressed versus non-depressed participants (IL-6, ρ = 0.027; tumor necrosis factor-alpha, ρ = 0.050; and recovery C-reactive protein, ρ = 0.003). It is concluded that depressed individuals display hyper-reactivity of neuroimmunological markers in response to acute negative emotions. This hyper-reactivity may serve a pathologic role in the elevated morbidity and mortality risk associated with depression.
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Major depression (MD) is a severe mental disorder characterized by alterations in mood and cognition, with disease severity correlating inversely with cognition scores. Neuropathology can be found abundantly in the limbic system, which is thought to regulate affect, attention and memory. Hypothalamic–pituitary–adrenal (HPA) axis overdrive, as well as decreased serotonin levels, have often been implicated in the pathogenesis of this illness. Interestingly, there is substantial interaction between these two systems, with receptors of one system influencing the function of the other. This results in impaired neural networks, which give rise to the wide range of depressive symptoms. Recently, it has been implied that MD could serve as a risk factor for developing Alzheimer's disease (AD), with patients suffering from lifetime depression having a twofold higher chance of developing AD and exhibiting more AD-related neuropathology. Modifications in the HPA-axis and the serotonergic system may contribute to the development of cognitive decline and eventually AD. These two systems may therefore be involved in the pathogenesis of both illnesses and could provide a link between MD and AD. Obtaining more knowledge on their interactive role in the relation between MD and AD may eventually aid in the development of more effective treatment strategies.
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Since then, diverse clinical studies have demonstrated that HPA axis hormones are altered in these patients (Carroll et al., 1976; Gold et al., 1986). Some studies demonstrate that the hipercortisolemia found in patients with major depression is due to a hypersecretion of corticotropin releasing factor (CRF) (Nemeroff et al., 1984) and adrenocorticotropic hormone (ACTH) (Kalin et al., 1982; Reus et al., 1982; Pfohl et al., 1985). However, although CRF is found to be elevated in most of depressive patients (Arborelius et al., 1999), data regarding ACTH concentrations are inconsistent: in some cases individuals with depression present high levels of ACTH but in other cases normal or even minor levels of ACTH are shown (Parker et al., 2003).
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^☆: Supported in part by NIMH Grant MH 34697 and the Clinical Research Center Program RR59.

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Biological Psychiatry

Abstract

References (31)

Plasma ACTH and cortisol levels in depressed patients: Relation to dexamethasone suppression test

Life Sci

Cortisol, 11-deoxycortisol, and ACTH concentrations after dexamethasone in depressed patients and healthy volunteers

Psychiatry Res

Plasma ACTH and cortisol concentrations before and after dexamethasone

Psychiatry Res

The influence of age on the cortisol response to dexamethasone

Psychiatry Res

Dexamethasone nonsuppression predicts the antidepressant effects of sleep deprivation

Psychiatry Res

Plasma ACTH levels in primary depression: relationship to the 24-hour dexamethasone suppression test

Psychiatry Res

The influence of weight loss on the Dexamethasone Suppression Test

Psychiatry Res

DSM III: Diagnostic and Statistical Manual of Mental Disorders

Influence of weight loss on the dexamethasone suppression test

Arch Gen Psychiatry

Neuroendocrine regulation in affective disorders

A specific laboratory test for the diagnosis of melancholia

Arch Gen Psychiatry

Neuroendocrine regulation in affective disorders

Antidepressant withdrawal and hypothalamic-pituitary-adrenal regulation

Effects of weight loss on the Dexamethasone Suppression Test

Am J Psychiatry

Paradoxical ACTH response to glucocorticoids in Cushing's disease

N Engl J Med

Cited by (86)

Alterations in chloride transporter activity in stress and depression

Age-Dependent and Gender-Dependent Regulation of Hypothalamic-Adrenocorticotropic-Adrenal Axis

Clinical utility of serum biomarkers for major psychiatric disorders

Neurohormonal and inflammatory hyper-responsiveness to acute mental stress in depression

Major depression, cognitive dysfunction and Alzheimer's disease: Is there a link?

Corticosterone as a marker of susceptibility to oxidative/nitrosative cerebral damage after stress exposure in rats

Differences in plasma ACTH and cortisol between depressed patients and normal controls☆

Abstract

Life Sci

Psychiatry Res

Psychiatry Res

Psychiatry Res

Psychiatry Res

Psychiatry Res

Psychiatry Res

DSM III: Diagnostic and Statistical Manual of Mental Disorders

Influence of weight loss on the dexamethasone suppression test

Arch Gen Psychiatry

Neuroendocrine regulation in affective disorders

A specific laboratory test for the diagnosis of melancholia

Arch Gen Psychiatry

Neuroendocrine regulation in affective disorders

Antidepressant withdrawal and hypothalamic-pituitary-adrenal regulation

Effects of weight loss on the Dexamethasone Suppression Test

Am J Psychiatry

Paradoxical ACTH response to glucocorticoids in Cushing's disease

N Engl J Med