NR3C1 Exon 1F Promoter Methylation and mRNA Expression in the Dorsolateral Prefrontal Cortex of Individuals Who Died by Suicide: A Post-Mortem Case–Control Study from Northern Mexico

Background: The glucocorticoid receptor gene (NR3C1) regulates hypothalamic–pituitary–adrenal (HPA) axis feedback. Evidence of its epigenetic and transcriptional alterations in suicide remains limited and inconsistent, particularly in underrepresented populations. Methods: We measured regional methylation within the assayed NR3C1 exon 1F promoter region and total NR3C1 mRNA expression in dorsolateral prefrontal cortex (BA9) from 13 suicide cases and 13 non-psychiatric controls from northern Mexico. Groups were frequency-matched by age, sex, and post-mortem interval. Methylation was assessed by methylation-sensitive restriction enzyme (MSRE) qPCR and expression by RT-qPCR. Group differences were tested using two-sided exact Mann–Whitney U tests; effect sizes were probability of superiority (PS) and Cliff’s δ. Correlation and male-only analyses were exploratory. All p-values were nominal. Results: Cases showed higher total NR3C1 mRNA expression (U = 45, p = 0.04412; PS = 0.734; δ = 0.467) and regional exon 1F methylation (U = 29, p = 0.00349; PS = 0.828; δ = 0.657). The measures showed a non-significant positive correlation (ρ = 0.27, p = 0.179). In males, methylation remained higher in cases (p = 0.0147), whereas expression remained directionally higher but non-significant (p = 0.165). Conclusions: Individuals who died by suicide showed higher regional exon 1F methylation and NR3C1 mRNA expression in BA9. The measures were not significantly correlated and should be interpreted as separate group-level differences, not evidence of direct methylation–expression coupling. The expression finding is preliminary. Given the small sample, limited clinical information, and comparison with non-psychiatric controls, the differences cannot be attributed specifically to suicide and require replication.