Pre-Existing High Glucocorticoid Receptor Number Predicting Development of Posttraumatic Stress Symptoms After Military Deployment
Abstract
OBJECTIVE: The development of posttraumatic stress disorder (PTSD) is influenced by preexisting vulnerability factors. The authors aimed at identifying a preexisting biomarker representing a vulnerability factor for the development of PTSD. To that end, they determined whether the dexamethasone binding capacity of leukocytes, as a measure of glucocorticoid receptor (GR) number, before exposure to trauma was a predictor of development of PTSD symptoms. In addition, the authors analyzed mRNA expression for GR subtypes and GR target genes. METHOD: Participants were selected from a large prospective study on deployment-related disorders, in which peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 and 6 months after military deployment. Participants included armed forces personnel with high levels of PTSD symptoms 6 months after deployment (N=34) and comparison subjects without high levels of PTSD or depressive symptoms (N=34) matched for age, rank, previous deployments, educational level, and function during deployment. RESULTS: Before military deployment, the GR number in PBMCs was significantly higher in participants who developed high levels of PTSD symptoms after deployment relative to matched comparison subjects. Logistic regression analysis showed that the risk for inclusion in the PTSD group after deployment increased 7.5-fold with each GR increase of 1,000. No group differences were observed in mRNA expression of GR-α, GR-P, GR-β, glucocorticoid-induced leucine zipper (GILZ), serum and glucocorticoid-inducible kinase-1 (SGK-1), and FKBP5. The higher GR number in the PTSD group was maintained at 1 and 6 months after deployment. CONCLUSIONS: These results demonstrate that a preexisting high GR number in PBMCs is a vulnerability factor for subsequent development of PTSD symptoms.
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Across survivor populations and their descendants, research suggests coordinated involvement of stress-response regulation, neurodevelopmental signaling, and behavioral adaptation.
“Across survivor populations and their descendants, research suggests coordinated involvement of stress-response regulation, neurodevelopmental signaling, and behavioral adaptation (7, 82–100).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [85]
Functional alterations in cortisol metabolism, including reduced cortisol excretion in survivors and increased activity of cortisol-inactivating enzymes in offspring, have been described.
“Functional alterations in cortisol metabolism, including reduced cortisol excretion in survivors and increased activity of cortisol-inactivating enzymes in offspring, have also been described (82, 85).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [85]
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- Authors
- van Zuiden, M., Geuze, E., Willemen, H. L. D. M., Vermetten, E., Maas, M., Heijnen, C. J., & Kavelaars, A.
- Affiliations
- From the Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht, the Netherlands; the Research Centre-Military Mental Health, Ministry of Defence, Utrecht, the Netherlands; and the Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
- University Medical Center Utrecht (NL)
- Venue
- American Journal of Psychiatry
- Published
- 2011-01
- Volume
- 168
- Issue
- 1
- Pages
- 89-96
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2120546159
- Cited by
- 190
- References
- 41
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 18 · 2021: 4 · 2020: 20 · 2019: 9 · 2018: 9 · 2017: 8 · 2016: 23 · 2015: 18 · 2014: 18 · 2013: 12 · 2012: 19
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- post-traumatic stress disorder, glucocorticoid receptor, leukocytes, military deployment, vulnerability factors, biomarkers, peripheral blood mononuclear cells, GILZ, SGK1, FKBP5, trauma exposure
- MeSH terms
- Tacrolimus Binding Protein 5, Serum-Glucocorticoid Regulated Kinases, Adult, Depression, Humans, Hydrocortisone, Male, Military Personnel, Receptors, Glucocorticoid, Risk Factors, Stress Disorders, Post-Traumatic, Transcription Factors, Biomarkers, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Tacrolimus Binding Proteins, Self Report
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