Childhood trauma dependent anxious depression sensitizes HPA axis function
Abstract
Anxious depression is a common subtype of major depressive disorder (MDD) and is associated with greater severity and poorer outcome. Alterations of the hypothalamic-pituitary-adrenal (HPA) axis, especially of the glucocorticoid receptor (GR) function, are often observed in MDD, but evidence lacks for anxious depression. Childhood adversity is known to influence both the HPA axis and risk of MDD. Therefore, we investigated GR-function in anxious depression dependent on childhood adversity. We enrolled 144 depressed in-patients (49.3% females). Anxious depression was defined using the Hamilton Depression Rating Scale (HAM-D) anxiety/somatization factor score ≥7. Blood draws were performed at 6 pm before and 3 h after 1.5 mg dexamethasone ingestion for measurement of cortisol, ACTH and blood count to assess GR-function and the immune system. In a subgroup of n = 60 FKBP5 mRNA controlled for FKBP5 genotype was measured before and after dexamethasone. Childhood adversity was evaluated using the Childhood Trauma Questionnaire (CTQ). We identified 78 patients (54.2%) with anxious depression who showed a greater severity and worse outcome. These patients were more often exposed to sexual abuse (30% vs. 16%/p = 0.04) and emotional neglect (76% vs. 58%/p = 0.02) than patients with non-anxious depression. Anxious depressed patients showed an enhanced GR-induced FKBP5 mRNA expression (F = 5.128; p = 0.03) and reduced cortisol levels, partly dependent on sexual abuse (F = 7.730; p = 0.006). Additionally, the GR-induced leukocyte response was enhanced in patients with sexual abuse (F = 7.176; p = 0.008). Anxious depression in dependence of childhood trauma is associated with heightened sensitivity of the HPA axis and the immune system which should be considered for treatment algorithms and targets.
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The mDST was able to identify HPA axis alterations in MDD, job-related exhaustion, anxious depression and childhood trauma, chronic stress, and healthy females compared to healthy men.
“The mDST was able to identify HPA axis alterations in MDD [67], job-related exhaustion [69], anxious depression and childhood trauma [70], chronic stress [31], and healthy females compared to healthy men [71].”
From The HPA Axis as Target for Depression (2024) · cites this paper as [70]
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Menke, A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00101 · Cited by 240 · see citing works
Self-citationThe HPA Axis as Target for Depression
Menke, A. (2024) · Current Neuropharmacology · doi:10.2174/1570159x21666230811141557 · Cited by 131 · see citing works
“The mDST was able to identify HPA axis alterations in MDD [67], job-related exhaustion [69], anx-ious depression and childhood trauma [70], chronic stress [31], and healthy females compared to healthy men [71].”
BackgroundSelf-citationMenke, A. (2018) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s146110 · Cited by 41 · see citing works
Self-citationStress impairs response to antidepressants via HPA axis and immune system activation
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- Authors
- Menke, A., Lehrieder, D., Fietz, J., Leistner, C., Wurst, C., Stonawski, S., Reitz, J., Lechner, K., Busch, Y., Weber, H., Deckert, J., & Domschke, K.
- Affiliations
- University of Würzburg (DE)
- Universitätsklinikum Würzburg (DE)
- University of Freiburg (DE)
- Corresponding author
- Menke, Andreas
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 98
- Pages
- 22-29
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2884221659
- Cited by
- 55
- References
- 17
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 5 · 2018: 2
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Julius-Maximilians-Universität Würzburg (N-355)
- Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- anxious depression, major depressive disorder, childhood trauma, hypothalamic-pituitary-adrenal axis, glucocorticoid receptor, FKBP5, dexamethasone suppression test, cortisol, ACTH, sexual abuse, emotional neglect, immune system, leukocyte response, depression severity, treatment goals
- MeSH terms
- Adverse Childhood Experiences, Tacrolimus Binding Protein 5, Adult, Anxiety, Anxiety Disorders, Depression, Major Depressive Disorder, Depressive Disorder, Major, Dexamethasone, Female, Glucocorticoids, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Inpatients, Male, Middle Aged, Pituitary-Adrenal System, Surveys and Questionnaires, Receptors, Glucocorticoid, Saliva, Tacrolimus Binding Proteins, Adult Survivors of Child Abuse
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