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

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  • Caroline Normann, Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.
  • ,
  • Henriette N. Buttenschøn

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.

Original languageEnglish
JournalActa Neuropsychiatrica
Pages (from-to)186-192
Publication statusPublished - Aug 2019

    Research areas

  • depression, gene-environment interaction, Key words:, life change events, polymorphism, psychological, single nucleotide, stress

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