Epigenomic alterations in psychiatric disorders and glioblastoma

Brain disorders are among the most debilitating, costly and therapeutically challenging conditions worldwide. Therefore, there is a growing need for identification of biomarkers to support diagnostic, prognostic and therapeutic procedures. Technological advances are enabling increasingly precise, high-throughput profiling of epigenetic modifications, and the potential reversibility of epigenetic marks makes them a promising target for therapeutic intervention. Recent research on in-vitro models, post-mortem brain samples and peripheral tissues from living individuals has suggested that epigenetic mechanisms are involved in the pathogenesis of chronic mental illnesses, functioning as distal or proximal risk factors and mediating the long-term effects of environmental stressors on brain function. In brain cancers, including the highly lethal glioblastoma, epigenetic dysregulation (especially DNA methylation patterns) is already implicated in tumor classification as it contributes to cellular heterogeneity and may drive tumor progression. This review examines the multifaceted role of epigenomic regulation of brain gene expression, focusing on psychiatric disorders and primary brain malignancies such as glioblastoma. We summarize the technological advances that have enabled high-throughput and high-resolution exploration of the epigenome. Furthermore, we present the current knowledge of epigenomic signatures that may contribute to brain pathology and discuss their potential for biomarker discovery and the advancement of personalized medicine.