Cited by 48Stress Responses and CortisolGenetic Associations and EpidemiologyNeurotransmitter Receptor Influence on Behavior

Gene–environment interactions between HPA-axis genes and stressful life events in depression: A systematic review

Normann, Caroline, Buttenschøn, Henriette N.·2019·Acta Neuropsychiatrica

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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Crossref · 10.1017/neu.2019.16

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Authors
Normann, C., & Buttenschøn, H. N.
Affiliations
Aarhus University (DK)
Corresponding author
Normann, Caroline
Venue
Acta Neuropsychiatrica
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

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