Epigenetic Modifications in Neuropsychiatric Disorders
Summary
Epigenetic mechanisms such as DNA methylation, histone modifications and chromatin remodelling exert crucial control over gene expression in the brain, shaping neurodevelopmental trajectories and synaptic plasticity. In neuropsychiatric disorders including schizophrenia, bipolar disorder, major depression and autism spectrum disorders, dysregulated epigenetic landscapes reflect the interaction between genetic susceptibility and environmental exposures. Specific patterns of cytosine methylation at promoter regions, dynamic histone methylation or acetylation marks and the recruitment of transcription factors define cell-type-specific transcriptional programmes in neurons and glia. Aberrant epigenetic signatures have been observed in peripheral tissues and post-mortem brain, linking processes such as inflammation, stress and metabolic dysregulation to altered neuronal function. Moreover, epigenetic variation mediates the impact of risk alleles by co-localising with genetic loci associated with disease and by modulating transcript levels of key synaptic and developmental genes. Understanding these modifications offers promise for biomarkers of diagnosis and treatment response, as well as the development of targeted epigenetic therapies that aim to restore precise chromatin states across diverse patient populations.
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Epigenetic Modifications in Neuropsychiatric Disorders publication trend
The graph below shows the total number of articles in epigenetic modifications in neuropsychiatric disorders across all publications each year (not limited to Nature Index journals).
Technical terms
DNA methylation: Addition of methyl groups to cytosine bases, often in CpG dinucleotides, influencing gene transcription.
Promoter region: DNA segment upstream of a gene that controls initiation of transcription.
Transcription factor: Protein that binds specific DNA sequences to regulate gene expression.
Biosignature: A set of molecular markers whose combined pattern correlates with a diagnostic or prognostic state.
Epigenome-wide association study (EWAS): Systematic analysis of epigenetic variation across the genome to identify associations with traits or diseases.
Differentially methylated position (DMP): Specific genomic locus where methylation levels differ significantly between groups.
References
- YBX1‐Mediated DNA Methylation‐Dependent SHANK3 Expression in PBMCs and Developing Cortical Interneurons in Schizophrenia. Advanced Science (2023).
- A novel blood-based epigenetic biosignature in first-episode schizophrenia patients through automated machine learning. Translational Psychiatry (2024).
- An integrated genetic-epigenetic analysis of schizophrenia: evidence for co-localization of genetic associations and differential DNA methylation. Genome Biology (2016).
- DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia. eLife (2021).
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