Short CommunicationThe dexamethasone corticotropin releasing hormone test in healthy and depressed women with and without childhood adversity
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.
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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.
References (19)
- et al.
Evaluation of a salivary based combined dexamethasone/CRH test in patients with major depression
Psychoneuroendocrinology
(2002) - et al.
Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment
Biol. Psychiatry
(2007) - et al.
Dex/CRH test cortisol response in outpatients with major depression and matched healthy controls
Psychoneuroendocrinology
(2009) - et al.
Effect of childhood emotional abuse and age on cortisol responsivity in adulthood
Biol. Psychiatry
(2009) - et al.
The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma
Biol. Psychiatry
(2008) - et al.
The combined dexamethasone/CRH test as a potential surrogate marker in depression
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2005) - et al.
Adulthood trauma and HPA-axis functioning in healthy subjects and PTSD patients: a meta-analysis
Psychoneuroendocrinology
(2012) - et al.
The role of specific early trauma in adult depression: a meta-analysis of published literature. Childhood trauma and adult depression
Eur. Psychiatry
(2015) - et al.
The DEX/CRH test for major depression: a potentially useful diagnostic test
Psychiatry Res.
(2013)