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Cited by 503Stress Responses and CortisolPosttraumatic Stress Disorder ResearchAdrenal Hormones and Disorders

Assessment of HPA axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review

de Kloet, C.S., Vermetten, E., Geuze, E., Kavelaars, A., Heijnen, C.J., Westenberg, H.G.M.·2006·Journal of Psychiatric Research
DOI 10.1016/j.jpsychires.2005.08.002
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Abstract

Posttraumatic stress disorder (PTSD) is typically accompanied by acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but several studies have also used a challenge model to further assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. This paper reviews common methodology and research findings on HPA function in PTSD, and discusses the pathophysiological mechanisms underlying these findings. We reviewed the literature and selected all English-language, human subject, data driven, pharmacological and non-pharmacological challenge studies pertaining to the HPA axis, and in vitro leukocyte glucocorticoid receptor studies in adult PTSD subjects. Studies using a non-pharmacological stress paradigm (cognitive stress, trauma reminders) to stimulate the HPA axis showed an exaggerated cortisol response in PTSD. The most widely used pharmacological challenge with consistent results was the low dose dexamethasone-suppression test (DST). These DST studies showed enhanced cortisol suppression in subjects with PTSD. Different hypotheses have been purported to explain the alterations in HPA axis functioning in PTSD. The results of the reviewed challenge tests, however, did not exclusively support one of the hypothesized mechanisms. Further research assessing hormones at all levels of the HPA axis at both baseline and at challenge conditions with a proper stratification of study population, will be necessary for a better understanding of stress-responsivity on the level of the HPA axis in PTSD.

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  • Chronic conditions such as coronary artery disease, fibromyalgia, rheumatoid arthritis, Major Depressive Disorder, and Post Traumatic Stress Disorder are associated with abnormally high cortisol levels and metabolic disruptions.

    “chronic conditions such as coronary artery disease, fibromyalgia, rheumatoid arthritis, and mood disorders such as Major Depressive Disorder (MDD) and Post Traumatic Stress Disorder (PTSD) have also been associated with abnormally high CORT levels and metabolic disruptions ( 5-13 ).”

    From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [10]

  • Many conditions associated with hypercortisolism are accompanied by disruption of normal glucose metabolism while preserving some degree of cortisol rhythmicity.

    “many of these conditions are accompanied by a disruption of normal glucose metabolism while preserving some degree of CORT rhythmicity.”

    From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [10]

  • In hypercortisolism, cortisol levels are higher than normal and in some cases display abnormal rhythmicity, varying by underlying condition.

    “in hypercortisolism, it is not only that CORT levels are higher than normal, but in some cases, they also display abnormal rhythmicity. This varies depending on whether the underlying condition is associated with Cushing's syndrome, depression, PTSD, acute inflammation following major surgery, or chronic inflammatory diseases (e.g., rheumatoid arthritis) ( 2, 5-13, 57-60 ).”

    From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [10]

  • Chronic persistent psychological distress can lead to increased sympathetic tone, decreased vagal tone, decreased heart rate variability, and increased arterial stiffness and endothelial dysfunction.

    “Chronic persistent psychological distress can also lead to increased sympathetic tone, decreased vagal tone, decreased heart rate variability, and increased arterial stiffness and endothelial dysfunction. 120-123”

    From Psychological Health, Well-Being, and the Mind-Heart-Body Connection: A Scientific Statement From the American Heart Association (2021) · cites this paper as [121]

  • HPA-axis dysregulation is not unique to depression and is observed in other disorders such as PTSD and social anxiety.

    “This is of great importance given that HPA-axis dysregulation is not unique to depression and is observed in many other disorders, such as post-traumatic stress disorder (de Kloet et al., 2006) and social anxiety (Beaton et al., 2006).”

    From Hypothalamic–pituitary–adrenal axis dysregulation in depressed children and adolescents: A meta-analysis (2009) · cites this paper as de Kloet et al., 2006

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Authors
de Kloet, C. S., Vermetten, E., Geuze, E., Kavelaars, A., Heijnen, C. J., & Westenberg, H. G. M.
Affiliations
  • Central Military Hospital (NL)
  • University Medical Center Utrecht (NL)
ORCID
Venue
Journal of Psychiatric Research
Publisher
Elsevier BV
Published
2006-09
Volume
40
Issue
6
Pages
550-567
ISSN
0022-3956 (ISSN-L)
DOI
10.1016/j.jpsychires.2005.08.002
OpenAlex
W2040975346
Cited by
503
References
71
Citations by year
2026: 11 · 2025: 11 · 2024: 16 · 2023: 14 · 2022: 17 · 2021: 23 · 2020: 33 · 2019: 19 · 2018: 36 · 2017: 31 · 2016: 32 · 2015: 54 · 2014: 21 · 2013: 22 · 2012: 29
FWCI
0.93
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Psychiatric Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
post-traumatic stress disorder, hypothalamic-pituitary-adrenal axis, HPA axis function, stress response, cortisol, dexamethasone suppression test, glucocorticoid receptor, trauma reminders, stress responsivity
MeSH terms
Cognition, Corticotropin-Releasing Hormone, Dexamethasone, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal Function Tests, Pituitary-Adrenal System, Stress Disorders, Post-Traumatic, Stress, Psychological, MEDLINE

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