Epigenomic analyses within postmortem brain tissue associated with posttraumatic stress disorder and depression

ABSTRACT: Molecular associations with psychiatric risk are being increasingly explored using peripheral cell types in patient populations. However, molecular analyses of brain regions implicated in risk are essential to providing insights into the antecedents and consequences of psychiatric disorder. In the current study we contrast the genome-wide DNA methylation levels of the amygdala, hippocampus, and prefrontal cortex using the Illumina EPIC array in the postmortem brain of individuals with a primary diagnosis of posttraumatic stress disorder (PTSD; N=101), major depressive disorder (MDD; N=101), and controls (N=100). Using cell type enrichment analyses, differential methylation analyses, multi-omics factor analysis (MOFA), rank-rank hypergeometic overlap analyses and Gene Set Enrichment Analysis (GSEA), we demonstrate: 1) the potential role of adult trauma exposure in PTSD-associated oligodendrocyte reductions in the amygdala, 2) the robust association of MDD with differential methylation within the amygdala that may be accounted for by variation in cell type enrichment in this brain region, 3) sex- and diagnosis-specific MOFA factors within the methylome that differentiate the immune and other biological pathways involved in PTSD, and 4) illustrate the lack of concordance in hyper- and hypo-methylation across brain regions in PTSD compared to MDD that may suggest highly brain region-specific molecular features of the PTSD brain. We also identify a novel brain-based biological aging factor using MOFA analyses that may provide insights into the biological pathways of brain aging. Overall, this work generates critical insights into the epigenetic manifestation of psychiatric risk.

ORGANISM(S): Homo sapiens

PROVIDER: GSE349373 | GEO | 2026/10/06

REPOSITORIES: GEO