Review
Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review

https://doi.org/10.1016/j.neubiorev.2015.05.016Get rights and content
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Highlights

  • NR3C1 gene methylation has been associated with early life stress.

  • NR3C1 gene methylation has been associated with psychosocial stress reactivity.

  • NR3C1 gene methylation correlates to NR3C1 expression.

  • Methodology differed greatly between papers reviewed.

  • Specific CpG site methylation may be more informative than mean methylation values.

Abstract

Early life stress (ELS) is a known risk factor for suffering psychopathology in adulthood. The hypothalamic–pituitary–adrenal (HPA) axis has been described to be deregulated in both individuals who experienced early psychosocial stress and in patients with a wide range of psychiatric disorders. The NR3C1 gene codes for the glucocorticoid receptor, a key element involved in several steps of HPA axis modulation. In this review, we gather existing evidence linking NR3C1 methylation pattern with either ELS or psychopathology. We summarize that several types of ELS have been frequently associated with NR3C1 hypermethylation whereas hypomethylation has been continuously found to be associated with post-traumatic stress disorder. In light of the reported findings, the main concerns of ongoing research in this field are the lack of methodological consensus and selection of CpG sites. Further studies should target individual CpG site methylation assessment focusing in biologically relevant areas such as transcription factor binding regions whereas widening the examined sequence in order to include all non-coding first exons of the NR3C1 gene in the analysis.

Keywords

DNA methylation
NR3C1 gene
Glucocorticoid receptor
Early life stress
Stress-related disorders

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