Elsevier

Psychoneuroendocrinology

Volume 87, January 2018, Pages 147-151
Psychoneuroendocrinology

Short Communication
The dexamethasone corticotropin releasing hormone test in healthy and depressed women with and without childhood adversity

https://doi.org/10.1016/j.psyneuen.2017.10.016Get rights and content

Highlights

  • To disentangle the effects of childhood adversity (ACE) and major depression (MDD) on HPA axis functioning.

  • 144 women (either with or without MDD and ACE, respectively) underwent the DEX/CRH test.

  • Free salivary cortisol responses were not significantly different between the four groups.

  • There was no evidence for a dysregulation of the HPA axis in depressed and healthy women with and without ACE, respectively.

Abstract

Background

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are a prominent finding in patients with major depressive disorder (MDD). Inconsistencies regarding a hyper- or hypoactive HPA axis may be explained by the moderating effect of childhood adverse experiences (ACE) which are associated with both HPA axis dysfunction and MDD in adulthood. We aimed to systematically disentangle the effects of ACE and MDD on HPA axis by comparing healthy women with and without childhood adversity and women with MDD with and without ACE.

Methods

The dexamethasone/corticotropin-releasing hormone (DEX/CRH) test was administered in 35 women with MDD and ACE as determined by a clinical interview (SCID, Early Trauma Inventory), 51 women with MDD without ACE, 21 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE.

Results

There were no group differences in age, smoking, body mass index, and intake of oral contraceptives. Free salivary cortisol responses were not significantly different between the four groups.

Conclusions

This study shows no evidence for a dysregulation of the HPA axis as measured by the DEX/CRH test in depressed women with and without childhood adversity as compared to mentally healthy women with or without early life stress. Our results do not support the assumption of distinct neuroendocrine endophenotypes in MDD with regard to ACE.

Introduction

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are often reported in neurobiological depression research. Correspondingly, studies using the dexamethasone/corticotropin-releasing hormone (DEX/CRH) test considered to be the most sensitive measure of HPA axis (Ising et al., 2005) have consistently demonstrated alterations in patients with a current episode of major depressive disorder (MDD) (Mokhtari et al., 2013). The majority of studies has reported an increased cortisol response to the Dex/CRH test in MDD as indicated by a characteristic “escape” from suppression with elevated ACTH and cortisol responses after CRH injection (Mokhtari et al., 2013). However, there is also some evidence for a blunted response of the HPA axis (Baumeister et al., 2014). For example, suicidal behavior in MDD was associated with attenuated rather than exaggerated cortisol responses to DEX/CRH (Pfennig et al., 2005). Further, significantly lower ACTH and cortisol levels in response to the DEX/CRH test were reported for depressed women on long-term sick-leave (Wahlberg et al., 2009). One study did not find any difference in DEX/CRH parameters between outpatients with current MDD and healthy controls (Carpenter et al., 2009a).

These inconsistencies may partially be explained by the moderating effect of childhood adversity which is associated with both HPA axis dysfunction and an increased risk to develop MDD in adulthood (Mandelli et al., 2015). There is mounting preclinical evidence that early adverse experiences (ACE), e.g. childhood abuse, lead to persistent changes in HPA axis function (Anacker et al., 2014). Recent studies in humans have also reported associations between ACE and enhanced or attenuated HPA axis function in both healthy individuals and depressed patients (Carpenter et al., 2007, Heim et al., 2008). One investigation that evaluated depressed men with the DEX/CRH test while considering the effects of ACE found that hormone responses associated with MDD differed as a function of childhood trauma history (Heim et al., 2008). A comparison of depressed patients with healthy controls on the DEX/CRH test found that patients reporting high levels of childhood emotional neglect had cortisol response patterns similar to those seen among healthy controls, while depressed patients without such histories had relatively elevated levels (Watson et al., 2007). In adults without major mental disorders, emotional abuse diminished cortisol response after the DEX/CRH test, independent of the effects of other types of childhood adversity (Carpenter et al., 2009b).

Considering that MDD and ACE are strongly related and that both are associated with HPA axis dysfunctions, our study aimed to systematically disentangle their differential effects on HPA axis reactivity as measured with the DEX/CRH test by comparing healthy women with and without childhood adversity and women with MDD with and without ACE.

Section snippets

Participants

The DEX/CRH test was administered to 144 women: 35 women with MDD and ACE (MDD+/ACE+), 51 women with MDD without ACE (MDD+/ACE−), 21 women with ACE but no current or lifetime MDD (MDD−/ACE+) and 37 healthy women who had never had any mental disorder and did not report sexual or physical abuse (MDD−/ACE−). ACE was defined as repeated sexual or physical abuse at least once a month over one year or more before age of 18.

Healthy participants with and without ACE were free of any current mental

Sample characteristics

Table 1 presents demographic and clinical data. There were no group differences in age, years of education, smoking, and intake of oral contraceptives. None of the controls and none of ACE group (MDD−/ACE+) took any psychotropic medication, whereas several patients with MDD received antidepressive medication. MDD patients with ACE did not differ in frequency of medication intake from MDD patients without ACE (p = 0.36).

By definition, none of the controls (MDD−/ACE−) and none of the ACE group

Discussion

Given the close association between major depression and childhood adversities and their impact on HPA axis function, we systematically investigated the effects of MDD and ACE on stress reactivity using a full factorial design with healthy women with and without severe ACE and women with MDD with and without ACE. We applied the DEX/CRH test, the most sensitive tool in HPA axis research in patients with MDD (Ising et al., 2005, Heim et al., 2008, Mokhtari et al., 2013). In contrast to our

Funding

The study was supported by a grant of the Deutsche Forschungsgemeinschaft (DFG; WI 3396/6-1 & SP 579/3-1) awarded to KW, CS and CO.

Conflict of interest

Dr. Otte has received honoraria fees for lectures from Lundbeck and Servier and has received compensation as a member of the scientific advisory board from Lundbeck and Neuraxpharm. Dr. Wingenfeld, Dr. Kuehl, Mrs. May, Dr. Schultebraucks, Dr. Hellmann-Regen and Dr. Spitzer, report no conflict of interest.

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