The significance of DNA methylation of the NR3C1 gene encoding the glucocorticoid receptor for developing resilience in individuals exposed to early life stress.

Abstract

Purpose: To analyze and interpret why some individuals are resilient to ELS while others are susceptible, resulting in psychiatric outcome later in life, with a focus on the role of DNAm of the NR3C1 gene as a mediating mechanism between ELS and the risk of psychiatric outcomes. We hypothesized that a high level of mental resilience to ELS, expressed as lower incidence of psychiatric outcomes, was associated with attenuated NR3C1 DNAm levels.

Materials and methods: The first authors conducted a systematic search on PubMed to identify primary research studies. Abstract were screened and full-text were reviewed to assess the eligibility for inclusion. Consensus on assessment was reached after discussion of eligibility criteria. Studies were sorted based on whether they investigated the association between ELS and NR3C1 DNAm in 1) individuals exposed compared to unexposed to ELS both without a psychiatric outcome or in 2) individuals exposed to ELS with a psychiatric outcome compared to exposed individuals without a psychiatric outcome.

Results and conclusion: Seven studies met the eligibility criteria. The results were inconsistent; two studies supported our hypothesis, two studies indicated that increased NR3C1 DNAm mediated resilience to ELS, and three studies found no association.