Sex-Specific Epigenomic Signatures of Stress Resilience and Vulnerability in the Brain

Stress-related neuropsychiatric disorders, such as depression, post-traumatic stress disorder (PTSD), and anxiety, manifest differently across sexes, with distinct prevalence rates and symptom profiles. While clinical evidence increasingly acknowledges sex as a critical determinant of stress susceptibility and resilience, the underlying epigenomic mechanisms remain incompletely defined. Epigenetic regulation - including DNA methylation, histone modifications, and chromatin accessibility - plays a central role in integrating hormonal, environmental, and genetic signals that shape brain plasticity. Recent discoveries highlight how sex hormones directly engage chromatin machinery in stress-responsive neural circuits and how X-linked epigenetic regulators and sex-biased non-coding RNA networks contribute to divergent transcriptional programs. However, significant gaps persist in understanding how these layers of regulation produce sex-specific outcomes or transmit epigenetic signals across generations.This Research Topic aims to illuminate the sex-specific epigenomic architecture of stress resilience and vulnerability in the brain. It seeks to delineate the molecular pathways through which sex hormones, non-coding RNAs, and chromatin dynamics converge to define adaptive or maladaptive responses to stress. By integrating multi-omics, cellular, and computational perspectives, this collection will address pivotal questions such as: How do sex differences emerge in stress-activated neural circuits through epigenomic remodeling? What developmental windows confer heightened vulnerability or resilience? Can peripheral or transgenerational epigenetic signatures serve as biomarkers for sex-dependent stress outcomes? Collectively, this Research Topic aspires to bridge mechanistic neuroepigenetics with translational insights relevant to mental health.To gather further insights into the sex-specific epigenomic bases of stress adaptation, we welcome contributions spanning molecular to systems-level analyses in the brain and related tissues. Submissions may include original research, reviews, mini reviews, and brief research reports. Topics of interest include, but are not limited to:Sex-stratified DNA methylation, histone modification, and chromatin accessibility profiling in stress-exposed neural tissuesMolecular and functional interactions between sex steroids and chromatin machinery along the hypothalamic–pituitary–adrenal (HPA) axisSex-biased non-coding RNA regulation of stress responsesSingle-cell and spatial epigenomic analyses to resolve cell-type-specific sex differences in stress adaptationDevelopmental and transgenerational programming of stress vulnerability and resiliencePeripheral epigenomic biomarkers reflecting sex-differentiated neuropsychiatric riskIntegrative computational and multi-omics approaches to model sex-specific regulatory networksArticle types accepted: Original Research, Review, Mini Review, and Brief Research Report. Topic editors: Mena Fatma, Nadine Provencal Source: https://www.frontiersin.org/research-topics/83771/sex-specific-epigenomic-signatures-of-stress-resilience-and-vulnerability-in-the-brain