Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene–environment interaction
Abstract
The hypothalamic-pituitary-adrenal (HPA)-axis regulates the response to stressful events and is expected to be involved in the pathogenesis of depression. The glucocorticoid receptor (GR) regulates the activity of the HPA-axis. Both GR gene polymorphisms and childhood adversity are known to be associated with increased risk for depression. In the Longitudinal Aging Study Amsterdam, a large population based sample of older men and women, 906 subjects were genotyped. An association study was performed to determine the relationship between GR gene polymorphisms, childhood adversity, HPA-axis markers and depressive symptoms. A gene-environment interaction between the GR polymorphisms 22/23EK and 9beta and childhood adversity resulted in an increased risk of clinically relevant depressive symptoms. Without childhood adversity no increased risk was present. The 22/23EK variant was also associated with a lower Free Cortisol Index in the presence of childhood adversity. Persons that are heterozygous for the BclI variant, in contrast with wild-type and BclI-homozygotes, had lower serum levels of cortisol binding globulin and had no increased risk of recurrent depressive symptoms in the presence of childhood adversity. We found a gene-environment (G x E) interaction between common variants of the GR gene and childhood adversity, demonstrating a vulnerable phenotype for developing clinically relevant depressive symptoms at old age. This G x E interaction also influenced HPA-axis markers…
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Bet et al. found that the 22/23EK variant was associated with a lower morning free cortisol index in subjects reporting childhood adversity.
“Moreover, the 22/23EK variant was associated with a lower morning free cortisol index in subjects reporting childhood adversity.”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Bet et al. (2009)
Bet et al. (2009) found that the 22/23 K and 9beta polymorphisms of NR3C1 interacted with childhood adversity to predict depressive symptoms in 906 older adults.
“The 22/23 K and 9beta polymorphisms interacted with childhood adversity to predict depressive symptoms.”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Bet et al. (2009)
Bet et al. found that in subjects reporting childhood adversity, heterozygotes for the Bcl1 variant had lower serum cortisol binding globulin and less risk of depressive symptoms than wild type or Bcl1 homozygous subjects.
“Also in subjects reporting childhood adversity, heterozygotes for the Bcl1 variant had lower serum cortisol binding globulin and less risk of depressive symptoms than either wild type or Bcl1 homozygous subjects.”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Bet et al. (2009)
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References 57 · Cited by 138
- Authors
- Bet, P. M., Penninx, B. W. J. H., Bochdanovits, Z., Uitterlinden, A. G., Beekman, A. T. F., van Schoor, N. M., Deeg, D. J. H., & Hoogendijk, W. J. G.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Erasmus MC (NL)
- Amsterdam Public Health (NL)
- Corresponding author
- Bet, Pierre M.
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2009-06-15
- Volume
- 150B
- Issue
- 5
- Pages
- 660-669
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2130034650
- Cited by
- 138
- References
- 57
- Citations by year
- 2026: 2 · 2025: 5 · 2023: 7 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 9 · 2015: 12 · 2014: 10 · 2013: 12 · 2012: 8
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- glucocorticoid receptor, genetic polymorphism, childhood adversity, depression, gene-environment interaction, hypothalamic-pituitary-adrenal axis, corticosteroid-binding globulin, free cortisol, older adults, depressive symptoms
- MeSH terms
- Aged, Aged, 80 and over, Depression, Disease Susceptibility, Environment, Epistasis, Genetic, Female, Gene Frequency, Humans, Life Change Events, Male, Middle Aged, Polymorphism, Genetic, Receptors, Glucocorticoid, Stress, Psychological, Linkage Disequilibrium, Adult Survivors of Child Abuse
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