RESUMEN
OBJECTIVE: Gene-environment (GxE) interactions may comprise an important part of the aetiology of depression, and childhood maltreatment (CM), a significant stressor, has consistently been linked to depression. Hence, in this systematic review, we aimed to investigate the interaction between hypothalamus-pituitary-adrenal axis (HPA-axis) genes and CM in depression. METHODS: We conducted a literature search using the Pubmed, Embase, and PsychINFO databases in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies investigating GxE interactions between HPA-axis genes [Angiotensin Converting Enzyme (ACE), Arginine Vasopressin (AVP), 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 CM in depression. RESULTS: The literature search identified 159 potentially relevant studies. Following screening, 138 of these were excluded. Thus, 21 studies, investigating a total of 51 single nucleotide polymorphisms, were included in the final study. The most prevalent genes in the current study were CRHR1 and FKBP5. Significant GxE interactions were reported in seven of eight studies for CRHR1:rs110402 and CM, and in five of eight studies for FKBP5:rs1360780 and CM. In summary, our results suggest possible GxE interactions between CRHR1, FKBP5, NR3C1, and NR3C2 and CM, respectively. For the remaining genes, no relevant literature emerged. CONCLUSIONS: We find that genetic variation in four HPA-axis genes may influence the effects of CM in depression.
RESUMEN
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.
