Histone Modifications in Psychiatry: From Canonical Marks to Neurotransmitter-Mediated Epigenetic Signatures

Histone modifications have emerged as critical epigenetic regulators in the development and progression of mental disorders. This review synthesizes recent advances in the field, highlighting both canonical modifications, such as methylation, acetylation, and phosphorylation, as well as novel discoveries that link neurotransmitter signaling to chromatin regulation. In particular, neurotransmitter-mediated histone modifications, including serotonylation, dopaminylation, and histaminylation, represent a compelling new paradigm by which neuronal activity and environmental stimuli can induce lasting changes in gene expression. Aberrant histone modifications have been implicated in the risk, symptomatology, and treatment response of psychiatric conditions such as depression, bipolar disorder, and schizophrenia. Furthermore, therapeutic strategies that target histone-modifying enzymes, most notably histone deacetylase inhibitors, are being actively explored for their potential to restore epigenetic balance and improve clinical outcomes. A deeper understanding of the mechanistic diversity and disease specificity of histone modifications will be crucial for the development of precision epigenetic therapies in psychiatry.