Gene–environment interactions between HPA-axis genes and stressful life events in depression: A systematic review
Abstract
OBJECTIVE: Depression is a disorder caused by genetics and environmental factors. The aim of this study was to perform a review investigating the interaction between genetic variations located in genes involved in hypothalamus-pituitary-adrenal axis (HPA-axis) and stressful life events (SLEs) in depression. METHODS: In this systematic review, we selected articles investigating the interaction between genes involved in the HPA-axis, such as Arginine Vasopressin (AVP), Angiotensin Converting Enzyme (ACE), Corticotrophin Releasing Hormone (CRH), Corticotrophin Releasing Hormone Receptor 1 (CRHR1), Corticotrophin Releasing Hormone Receptor 2 (CRHR2), FK506 binding protein (FKBP5), Nuclear Receptor subfamily 3 group C member 1 (NR3C1), Nuclear Receptor subfamily 3 group C member 2 (NR3C2), and SLE. The literature search was conducted using the Pubmed, Embase, and PsychINFO databases in adherence with the PRISMA guidelines. RESULTS: The search yielded 48 potentially relevant studies, of which 40 were excluded following screening. Eight studies were included in the final review. A total of 97 single nucleotide polymorphisms (SNPs) were examined in the eight included studies. The most prevalent gene was FKBP5, and the best studied polymorphism was FKBP5:rs1360780. Two of the five studies reported significant gene-environment (G × E) interactions between rs1360780 and SLE. Overall, four studies reported significant G × E interactions between FKBP5, CRH, or CRHR1 and SLE, respectively. No significant G × E interactions were found for the remaining genes. CONCLUSIONS: Our results suggest that genetic variation in three genes in the HPA-axis possibly moderate the effects of SLEs in depression.
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Genetic variation of HPA-axis genes moderates the relationship between stressors and depression.
“Other research reported that the genetic variation of HPA-axis genes has moderating effects on the relationship between stressors and depression [198].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [198]
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- Authors
- Normann, C., & Buttenschøn, H. N.
- Affiliations
- Aarhus University (DK)
- Corresponding author
- Normann, Caroline
- Venue
- Acta Neuropsychiatrica
- Publisher
- Cambridge University Press (CUP)
- Published
- 2019-05-20
- Volume
- 31
- Issue
- 04
- Pages
- 186-192
- ISSN
- 0924-2708 (ISSN-L)
- 1601-5215
- OpenAlex
- W2946196574
- Cited by
- 48
- References
- 48
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 14
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Neuropsychiatrica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- depression, gene-environment interaction, hypothalamic-pituitary-adrenal axis, life events, FKBP5, rs1360780, corticotropin-releasing factor, CRH receptor 1, CRH receptor 2, vasopressin, angiotensin-converting enzyme, NR3C1, mineralocorticoid receptor, single nucleotide polymorphisms, genetic susceptibility
- MeSH terms
- Tacrolimus Binding Protein 5, Depressive Disorder, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Stress, Psychological, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins, Gene-Environment Interaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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