Glucocorticoid Receptor Pathway Components Predict Posttraumatic Stress Disorder Symptom Development: A Prospective Study
Abstract
Background Biological correlates of posttraumatic stress disorder (PTSD) have mostly been studied using cross-sectional or posttrauma prospective designs. Therefore, it remains largely unknown whether previously observed biological correlates of PTSD precede trauma exposure. We investigated whether glucocorticoid receptor (GR) pathway components assessed in leukocytes before military deployment represent preexisting vulnerability factors for development of PTSD symptoms.Methods Four hundred forty-eight male soldiers were assessed before and 6 months after deployment to a combat zone. Participants were assigned to the PTSD or comparison group based on Self-Rating Inventory for PTSD scores after deployment. Logistic regression analysis was applied to predict development of a high level of PTSD symptoms based on predeployment GR number, messenger (m)RNA expression of GR target genes FKBP5, GILZ, and SGK1, plasma cortisol, and childhood trauma. We also investigated whether predeployment GR number and FKBP5 mRNA expression were associated with single nucleotide polymorphisms in the GR and FKBP5 genes, either alone or in interaction with childhood trauma.Results Several GR pathway components predicted subsequent development of a high level of PTSD symptoms: predeployment high GR number, low FKBP5 mRNA expression, and high GILZ mRNA expression were independently associated with increased risk for a high level of PTSD symptoms. Childhood trauma also independently predicted development of a high level of PTSD symptoms. Additionally, we observed a significant interaction effect of GR haplotype BclI and childhood trauma on GR number.Conclusions Collectively, our results indicate that predeployment GR pathway components are vulnerability factors for subsequent development of a high level of PTSD symptoms.
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Increased risk of PTSD development is associated with pre-existing dysregulations of (para)sympathetic and hypothalamic-pituitary-adrenal axes.
“An increased risk of PTSD development is associated with pre-existing dysregulations of (para)sympathetic [17,18] and hypothalamic-pituitary-adrenal axes [20,21], as well as dysregulations of central fear responses prior to [22] and shortly after trauma exposure [23,24].”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [20]
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- Authors
- van Zuiden, M., Geuze, E., Willemen, H. L. D. M., Vermetten, E., Maas, M., Amarouchi, K., Kavelaars, A., & Heijnen, C. J.
- Affiliations
- University Medical Center Utrecht (NL)
- Corresponding author
- Heijnen, Cobi J.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 71
- Issue
- 4
- Pages
- 309-316
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2086152675
- Cited by
- 201
- References
- 58
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 2 · 2023: 8 · 2022: 11 · 2021: 8 · 2020: 21 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 23 · 2015: 23 · 2014: 17 · 2013: 24 · 2012: 10
- FWCI
- 17.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dutch Ministry of Defence
- 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, FKBP5, GILZ, SGK1, childhood trauma, genetic polymorphism, vulnerability factors, combat deployment, military personnel, plasma cortisol
- MeSH terms
- Tacrolimus Binding Protein 5, Combat Disorders, Genetic Testing, Humans, Hydrocortisone, Male, Psychiatric Status Rating Scales, Receptors, Glucocorticoid, Risk Factors, RNA, Messenger, Stress Disorders, Post-Traumatic, Transcription Factors, Gene Expression, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins, Adult Survivors of Child Abuse, Young Adult
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